Digital quantitative assessment of PD-L1 using digital spatial profiling

The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays u...

Full description

Saved in:
Bibliographic Details
Published in:Laboratory investigation Vol. 100; no. 10; pp. 1311 - 1317
Main Authors: Gupta, Swati, Zugazagoitia, Jon, Martinez-Morilla, Sandra, Fuhrman, Kit, Rimm, David L.
Format: Journal Article
Language:English
Published: New York Elsevier Inc 01.10.2020
Nature Publishing Group US
Nature Publishing Group
Subjects:
ISSN:0023-6837, 1530-0307, 1530-0307
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA-approved PD-L1 assays, one LDT assay and three quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various ranges of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using the GeoMx DSP assay and read on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy. Digital spatial profiling is a new high-plex technology with potential to multiplex hundreds of proteins on a single slide. Here the authors validate the digital aspect of the technology on a control tissue microarray with known amounts of PD-L1 expression to show it has quantitative capacity comparable to quantitative immunofluorescence.
AbstractList The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA-approved PD-L1 assays, one LDT assay and three quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various ranges of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using the GeoMx DSP assay and read on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy.The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA-approved PD-L1 assays, one LDT assay and three quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various ranges of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using the GeoMx DSP assay and read on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy.
The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA-approved PD-L1 assays, one LDT assay and three quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various ranges of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using the GeoMx DSP assay and read on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy.Digital spatial profiling is a new high-plex technology with potential to multiplex hundreds of proteins on a single slide. Here the authors validate the digital aspect of the technology on a control tissue microarray with known amounts of PD-L1 expression to show it has quantitative capacity comparable to quantitative immunofluorescence.
The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA-approved PD-L1 assays, one LDT assay and three quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various ranges of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using the GeoMx DSP assay and read on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy. Digital spatial profiling is a new high-plex technology with potential to multiplex hundreds of proteins on a single slide. Here the authors validate the digital aspect of the technology on a control tissue microarray with known amounts of PD-L1 expression to show it has quantitative capacity comparable to quantitative immunofluorescence.
The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA approved PD-L1 assay and one LDT assay and 3 quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various range of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using GeoMx DSP assay and readout on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy. Digital spatial profiling is a new high-plex technology with potential to multiplex hundreds of proteins on a single slide. Here the authors validate the digital aspect of the technology on a control tissue microarray with known amounts of PD-L1 expression to show it has quantitative capacity comparable to quantitative immunofluorescence.
The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA-approved PD-L1 assays, one LDT assay and three quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various ranges of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using the GeoMx DSP assay and read on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy.
Author Gupta, Swati
Martinez-Morilla, Sandra
Zugazagoitia, Jon
Fuhrman, Kit
Rimm, David L.
AuthorAffiliation 1 Department of Pathology, Yale University School of Medicine, New Haven, CT
2 Nanostring Technologies®, Seattle, WA
3 Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT
AuthorAffiliation_xml – name: 1 Department of Pathology, Yale University School of Medicine, New Haven, CT
– name: 3 Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT
– name: 2 Nanostring Technologies®, Seattle, WA
Author_xml – sequence: 1
  givenname: Swati
  surname: Gupta
  fullname: Gupta, Swati
  organization: Department of Pathology, Yale University School of Medicine, New Haven, CT, US
– sequence: 2
  givenname: Jon
  surname: Zugazagoitia
  fullname: Zugazagoitia, Jon
  organization: Department of Pathology, Yale University School of Medicine, New Haven, CT, US
– sequence: 3
  givenname: Sandra
  surname: Martinez-Morilla
  fullname: Martinez-Morilla, Sandra
  organization: Department of Pathology, Yale University School of Medicine, New Haven, CT, US
– sequence: 4
  givenname: Kit
  surname: Fuhrman
  fullname: Fuhrman, Kit
  organization: Nanostring Technologies®, Seattle, WA, US
– sequence: 5
  givenname: David L.
  orcidid: 0000-0001-5820-4397
  surname: Rimm
  fullname: Rimm, David L.
  email: david.rimm@yale.edu
  organization: Department of Pathology, Yale University School of Medicine, New Haven, CT, US
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32249818$$D View this record in MEDLINE/PubMed
BookMark eNp9kU9v1DAQxS3Uim4LH4ALisSFS6jHf-JESEioBVppJTjA2fI648VV1t7ayUp8e7xkC7SHPY3teb_R87xzchJiQEJeAX0HlLeXWQBXoqaM1lQwUctnZAGSlxun6oQsKGW8blquzsh5zneUghCNfE7OOGOia6FdkJtrv_ajGar7yYSxnEa_w8rkjDlvMIxVdNW363oJ1ZR9WFf9QZ63RVnqNkXnh9J5QU6dGTK-PNQL8uPzp-9XN_Xy65fbq4_L2krGxhocNtiBBWUUKtczZRiViq9aZrgr76xvVOOs7cFxJl0PABJUy0G0zUp0_IJ8mOdup9UGe1s8JjPobfIbk37paLx-3An-p17HnVaSMsGbMuDtYUCK9xPmUW98tjgMJmCcsma8bYSkQEWRvnkivYtTCuV7mgkluo52jBXV6_8d_bXysOQiULPApphzQqftn0XHvUE_aKB6H6ee49QlTr2PU8tCwhPyYfgxhs1MLtqwxvTP9DHo_QxhiW7nC5Stx2Cx9wntqPvoj9C_AZeww_I
CitedBy_id crossref_primary_10_1136_jcp_2024_209766
crossref_primary_10_1631_jzus_B2200605
crossref_primary_10_3390_cancers14194923
crossref_primary_10_3390_cancers12092572
crossref_primary_10_1016_j_eururo_2023_11_008
crossref_primary_10_1038_s41571_021_00520_1
crossref_primary_10_3389_fonc_2022_890410
crossref_primary_10_1016_j_lungcan_2023_107230
crossref_primary_10_3389_fimmu_2022_920021
crossref_primary_10_1186_s42047_025_00177_5
crossref_primary_10_3390_cancers14153833
crossref_primary_10_1158_1078_0432_CCR_21_0343
crossref_primary_10_1158_1078_0432_CCR_24_2469
crossref_primary_10_3389_fimmu_2022_996721
crossref_primary_10_1136_jitc_2022_006234
crossref_primary_10_1007_s00259_024_06610_3
crossref_primary_10_1038_s41467_023_37806_0
crossref_primary_10_3390_cancers13010029
crossref_primary_10_1038_s41467_021_27723_5
crossref_primary_10_1158_1078_0432_CCR_24_0853
crossref_primary_10_1007_s00761_021_01070_y
crossref_primary_10_1093_jnen_nlab122
crossref_primary_10_1007_s12035_022_03031_x
crossref_primary_10_1016_j_ijbiomac_2024_129551
crossref_primary_10_1146_annurev_biodatasci_102523_103640
Cites_doi 10.1200/JCO.2015.63.7421
10.1038/s41598-017-17204-5
10.1136/jclinpath-2018-205362
10.1016/S0140-6736(15)01281-7
10.1158/1078-0432.CCR-19-0104
10.1038/modpathol.2017.59
10.1038/modpathol.2017.188
10.1158/1535-7163.MCT-14-0983
10.1056/NEJMoa1200694
10.1002/cncr.25747
10.1016/j.jtho.2017.11.112
10.1016/j.jtho.2016.11.2228
10.1158/1078-0432.CCR-16-2375
10.1016/j.jtho.2018.05.013
10.1056/NEJMoa1709937
10.1200/JCO.2017.74.3062
10.1001/jamaoncol.2017.0013
10.1126/science.aaa8172
10.1016/j.jtho.2017.11.123
10.1001/jamaoncol.2016.3015
10.1101/559021
ContentType Journal Article
Copyright 2020 United States & Canadian Academy of Pathology
The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2020
The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2020.
Copyright_xml – notice: 2020 United States & Canadian Academy of Pathology
– notice: The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2020
– notice: The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2020.
DBID 6I.
AAFTH
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7QL
7QP
7QR
7T5
7T7
7TK
7TM
7U9
7X7
7XB
88E
8AO
8C1
8FD
8FE
8FH
8FI
8FJ
8FK
ABUWG
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
C1K
CCPQU
DWQXO
FR3
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
LK8
M0S
M1P
M7N
M7P
P64
PHGZM
PHGZT
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
7X8
5PM
DOI 10.1038/s41374-020-0424-5
DatabaseName ScienceDirect Open Access Titles
Elsevier:ScienceDirect:Open Access
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Calcium & Calcified Tissue Abstracts
Chemoreception Abstracts
Immunology Abstracts
Industrial and Applied Microbiology Abstracts (Microbiology A)
Neurosciences Abstracts
Nucleic Acids Abstracts
Virology and AIDS Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest Pharma Collection
Public Health Database
Technology Research Database
ProQuest SciTech Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials - QC
Biological Science Collection
ProQuest Central
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
ProQuest Central Korea
Engineering Research Database
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
ProQuest Biological Science Collection
ProQuest Health & Medical Collection
Medical Database
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biological Science Database
Biotechnology and BioEngineering Abstracts
Proquest Central Premium
ProQuest One Academic (New)
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic (retired)
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
ProQuest Central Student
ProQuest Central Essentials
Nucleic Acids Abstracts
SciTech Premium Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest One Applied & Life Sciences
Health Research Premium Collection
Natural Science Collection
Health & Medical Research Collection
Biological Science Collection
Chemoreception Abstracts
Industrial and Applied Microbiology Abstracts (Microbiology A)
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
Neurosciences Abstracts
ProQuest Hospital Collection (Alumni)
Biotechnology and BioEngineering Abstracts
ProQuest Health & Medical Complete
ProQuest One Academic UKI Edition
Engineering Research Database
ProQuest One Academic
Calcium & Calcified Tissue Abstracts
ProQuest One Academic (New)
Technology Research Database
ProQuest One Academic Middle East (New)
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Pharma Collection
ProQuest Central
ProQuest Health & Medical Research Collection
Health and Medicine Complete (Alumni Edition)
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
ProQuest Public Health
ProQuest SciTech Collection
ProQuest Medical Library
Immunology Abstracts
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
ProQuest Central Student



MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1530-0307
EndPage 1317
ExternalDocumentID PMC7502436
32249818
10_1038_s41374_020_0424_5
S0023683722003531
Genre Research Support, Non-U.S. Gov't
Journal Article
GrantInformation_xml – fundername: Breast Cancer Research Foundation (BCRF)
  grantid: BCRF-19-138
  funderid: https://doi.org/10.13039/100001006
– fundername: NCI NIH HHS
  grantid: P50 CA196530
– fundername: NCI NIH HHS
  grantid: P30 CA016359
– fundername: NCATS NIH HHS
  grantid: UL1 TR001863
GroupedDBID ---
-Q-
-~X
.55
.GJ
0R~
1KJ
29L
2WC
36B
39C
3V.
4.4
53G
5GY
5RE
6I.
70F
7X7
88E
8AO
8C1
8FI
8FJ
8R4
8R5
8WZ
A6W
AADWK
AAFTH
AANZL
AAWBL
AAXUO
AAYFA
AAYJO
AAZLF
ABAWZ
ABCQX
ABGIJ
ABJNI
ABLJU
ABUWG
ACBMV
ACBRV
ACBYP
ACGFO
ACGFS
ACIGE
ACIWK
ACKTT
ACPRK
ACRQY
ACTTH
ACVWB
ACZOJ
ADBBV
ADHDB
ADMDM
ADQMX
ADYYL
AEDAW
AEFTE
AEJRE
AENEX
AEXYK
AFFNX
AFKRA
AFOSN
AFRAH
AFSHS
AGAYW
AGEZK
AGGBP
AGHAI
AHMBA
AHPSJ
AHSBF
AILAN
AJDOV
AJRNO
ALFFA
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
AMRJV
AMYLF
ASPBG
AVWKF
AXYYD
AZFZN
BAWUL
BBNVY
BENPR
BHPHI
BKKNO
BPHCQ
BVXVI
CAG
CCPQU
COF
CS3
DIK
DNIVK
DU5
E3Z
EBLON
EBS
EE.
EIOEI
EJD
EMB
F5P
FDB
FDQFY
FEDTE
FERAY
FIZPM
FSGXE
FYUFA
GX1
HCIFZ
HMCUK
HVGLF
HZ~
IH2
IWAJR
JSO
JZLTJ
KQ8
M1P
M7P
MVM
NAO
NQJWS
NYICJ
O9-
OK1
P2P
P6G
PQQKQ
PROAC
PSQYO
Q2X
RNS
RNT
RNTTT
ROL
S10
SNX
SNYQT
SOHCF
SRMVM
SV3
SWTZT
TAOOD
TBHMF
TDRGL
TR2
TSG
TWZ
UKHRP
X7M
Y6R
YFH
YKV
YOC
YQI
YQT
ZA5
ZGI
ZXP
AAHOK
AALRI
ADVLN
AFJKZ
AITUG
AKRWK
ALIPV
PKN
AAYWO
AAYXX
ACVFH
ADCNI
ADXHL
AEUPX
AFFHD
AFPUW
AIGII
AKBMS
AKYEP
APXCP
CITATION
EFKBS
PHGZM
PHGZT
PJZUB
PPXIY
PQGLB
AGCQF
CGR
CUY
CVF
ECM
EIF
NPM
7QL
7QP
7QR
7T5
7T7
7TK
7TM
7U9
7XB
8FD
8FE
8FH
8FK
AZQEC
C1K
DWQXO
FR3
GNUQQ
H94
K9.
LK8
M7N
P64
PKEHL
PQEST
PQUKI
PRINS
7X8
PUEGO
5PM
ID FETCH-LOGICAL-c522t-1fe6e91c17a7e7fd27a20573b82a3f1c12d676fccd1f325fd111517831486b493
IEDL.DBID 7X7
ISICitedReferencesCount 26
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000523949500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 0023-6837
1530-0307
IngestDate Tue Nov 04 01:56:18 EST 2025
Sat Sep 27 22:07:30 EDT 2025
Mon Oct 06 16:56:19 EDT 2025
Mon Jul 21 06:02:15 EDT 2025
Sat Nov 29 01:48:22 EST 2025
Tue Nov 18 21:08:04 EST 2025
Fri Feb 21 02:38:04 EST 2025
Fri Feb 23 02:39:23 EST 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 10
Language English
License This article is made available under the Elsevier license.
Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c522t-1fe6e91c17a7e7fd27a20573b82a3f1c12d676fccd1f325fd111517831486b493
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
AUTHORS’ CONTRIBUTION
DLR and SG conceived the study, supervised the analysis and revised the final version of the manuscript. SG and JZ selected the study specimens and carried out the GeoMx DSP data analysis. SG drafted the manuscript. KF performed the GeoMx DSP assay. SMM carried out fluorescent and chromogenic IHC assay. All authors have read and approved the final version of the manuscript.
ORCID 0000-0001-5820-4397
OpenAccessLink https://pubmed.ncbi.nlm.nih.gov/PMC7502436
PMID 32249818
PQID 2474990922
PQPubID 25033
PageCount 7
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_7502436
proquest_miscellaneous_2386450104
proquest_journals_2474990922
pubmed_primary_32249818
crossref_citationtrail_10_1038_s41374_020_0424_5
crossref_primary_10_1038_s41374_020_0424_5
springer_journals_10_1038_s41374_020_0424_5
elsevier_sciencedirect_doi_10_1038_s41374_020_0424_5
PublicationCentury 2000
PublicationDate 2020-10-01
PublicationDateYYYYMMDD 2020-10-01
PublicationDate_xml – month: 10
  year: 2020
  text: 2020-10-01
  day: 01
PublicationDecade 2020
PublicationPlace New York
PublicationPlace_xml – name: New York
– name: United States
PublicationSubtitle Advancing the understanding of human and experimental disease
PublicationTitle Laboratory investigation
PublicationTitleAbbrev Lab Invest
PublicationTitleAlternate Lab Invest
PublicationYear 2020
Publisher Elsevier Inc
Nature Publishing Group US
Nature Publishing Group
Publisher_xml – name: Elsevier Inc
– name: Nature Publishing Group US
– name: Nature Publishing Group
References Merritt CR, Ong GT, Church S, Barker K, Geiss G, Hoang M, et al. High multiplex, digital spatial profiling of proteins and RNA in fixed tissue using genomic detection methods. bioRxiv. 2019.
Herbst, Baas, Kim, Felip, Perez-Gracia, Han (bib2) 2016; 387
McDermott, Sosman, Sznol, Massard, Gordon, Hamid (bib4) 2016; 34
Brunnstrom, Johansson, Westbom-Fremer, Backman, Djureinovic, Patthey (bib17) 2017; 30
Antonia, Villegas, Daniel, Vicente, Murakami, Hui (bib1) 2017; 377
Patel, Kurzrock (bib5) 2015; 14
Brahmer, Tykodi, Chow, Hwu, Topalian, Hwu (bib6) 2012; 366
Toki, Merritt, Wong, Smithy, Kluger, Syrigos (bib19) 2019; 25
Gaule, Smithy, Toki, Rehman, Patell-Socha, Cougot (bib15) 2017; 3
Gadiot, Hooijkaas, Kaiser, van Tinteren, van Boven, Blank (bib7) 2011; 117
Tsao, Kerr, Kockx, Beasley, Borczuk, Botling (bib16) 2018; 13
.
Ratcliffe, Sharpe, Midha, Barker, Scott, Scorer (bib13) 2017; 23
Hendry, Byrne, Wright, Young, Sturrock, Cooper (bib11) 2018; 13
Sharma, Allison (bib21) 2015; 348
Batenchuk, Albitar, Zerba, Sudarsanam, Chizhevsky, Jin (bib8) 2018; 71
Hirsch, McElhinny, Stanforth, Ranger-Moore, Jansson, Kulangara (bib14) 2017; 12
Rimm, Han, Taube, Yi, Bridge, Flieder (bib12) 2017; 3
Tretiakova, Fulton, Kocherginsky, Long, Ussakli, Antic (bib9) 2018; 31
Horn, Spigel, Vokes, Holgado, Ready, Steins (bib3) 2017; 35
Fujimoto, Sato, Uehara, Ishida, Fukuoka, Morimoto (bib10) 2018; 13
Bankhead, Loughrey, Fernandez, Dombrowski, McArt, Dunne (bib20) 2017; 7
Antonia, Villegas, Daniel, Vicente, Murakami, Hui (CR1) 2017; 377
Horn, Spigel, Vokes, Holgado, Ready, Steins (CR3) 2017; 35
Gaule, Smithy, Toki, Rehman, Patell-Socha, Cougot (CR15) 2017; 3
Patel, Kurzrock (CR5) 2015; 14
Tsao, Kerr, Kockx, Beasley, Borczuk, Botling (CR16) 2018; 13
CR18
Hendry, Byrne, Wright, Young, Sturrock, Cooper (CR11) 2018; 13
Gadiot, Hooijkaas, Kaiser, van Tinteren, van Boven, Blank (CR7) 2011; 117
Hirsch, McElhinny, Stanforth, Ranger-Moore, Jansson, Kulangara (CR14) 2017; 12
Toki, Merritt, Wong, Smithy, Kluger, Syrigos (CR19) 2019; 25
McDermott, Sosman, Sznol, Massard, Gordon, Hamid (CR4) 2016; 34
Tretiakova, Fulton, Kocherginsky, Long, Ussakli, Antic (CR9) 2018; 31
Fujimoto, Sato, Uehara, Ishida, Fukuoka, Morimoto (CR10) 2018; 13
Rimm, Han, Taube, Yi, Bridge, Flieder (CR12) 2017; 3
Bankhead, Loughrey, Fernandez, Dombrowski, McArt, Dunne (CR20) 2017; 7
Brunnstrom, Johansson, Westbom-Fremer, Backman, Djureinovic, Patthey (CR17) 2017; 30
Herbst, Baas, Kim, Felip, Perez-Gracia, Han (CR2) 2016; 387
Ratcliffe, Sharpe, Midha, Barker, Scott, Scorer (CR13) 2017; 23
Batenchuk, Albitar, Zerba, Sudarsanam, Chizhevsky, Jin (CR8) 2018; 71
Brahmer, Tykodi, Chow, Hwu, Topalian, Hwu (CR6) 2012; 366
Sharma, Allison (CR21) 2015; 348
Horn (10.1038/s41374-020-0424-5_bib3) 2017; 35
McDermott (10.1038/s41374-020-0424-5_bib4) 2016; 34
Bankhead (10.1038/s41374-020-0424-5_bib20) 2017; 7
Antonia (10.1038/s41374-020-0424-5_bib1) 2017; 377
Patel (10.1038/s41374-020-0424-5_bib5) 2015; 14
Tsao (10.1038/s41374-020-0424-5_bib16) 2018; 13
Tretiakova (10.1038/s41374-020-0424-5_bib9) 2018; 31
Batenchuk (10.1038/s41374-020-0424-5_bib8) 2018; 71
Hirsch (10.1038/s41374-020-0424-5_bib14) 2017; 12
Gaule (10.1038/s41374-020-0424-5_bib15) 2017; 3
Toki (10.1038/s41374-020-0424-5_bib19) 2019; 25
Fujimoto (10.1038/s41374-020-0424-5_bib10) 2018; 13
Brunnstrom (10.1038/s41374-020-0424-5_bib17) 2017; 30
Hendry (10.1038/s41374-020-0424-5_bib11) 2018; 13
Rimm (10.1038/s41374-020-0424-5_bib12) 2017; 3
10.1038/s41374-020-0424-5_bib18
Herbst (10.1038/s41374-020-0424-5_bib2) 2016; 387
Ratcliffe (10.1038/s41374-020-0424-5_bib13) 2017; 23
Sharma (10.1038/s41374-020-0424-5_bib21) 2015; 348
Brahmer (10.1038/s41374-020-0424-5_bib6) 2012; 366
Gadiot (10.1038/s41374-020-0424-5_bib7) 2011; 117
References_xml – volume: 366
  start-page: 2455
  year: 2012
  end-page: 2465
  ident: bib6
  article-title: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
  publication-title: N Engl J Med
– volume: 25
  start-page: 5503
  year: 2019
  ident: bib19
  article-title: High-plex predictive marker discovery for melanoma immunotherapy-treated patients using digital spatial profiling
  publication-title: Clin Cancer Res
– volume: 34
  start-page: 833
  year: 2016
  end-page: 842
  ident: bib4
  article-title: Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study
  publication-title: J Clin Oncol
– volume: 14
  start-page: 847
  year: 2015
  end-page: 856
  ident: bib5
  article-title: PD-L1 expression as a predictive biomarker in cancer immunotherapy
  publication-title: Mol Cancer Ther
– volume: 3
  start-page: 256
  year: 2017
  ident: bib15
  article-title: A quantitative comparison of antibodies to programmed cell death 1 ligand 1
  publication-title: JAMA Oncol
– volume: 13
  start-page: 367
  year: 2018
  ident: bib11
  article-title: Comparison of four PD-L1 immunohistochemical assays in lung cancer
  publication-title: J Thorac Oncol
– volume: 3
  start-page: 1051
  year: 2017
  end-page: 1058
  ident: bib12
  article-title: A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer
  publication-title: JAMA Oncol
– volume: 13
  start-page: 377
  year: 2018
  ident: bib10
  article-title: Predictive performance of four programmed cell death ligand 1 assay systems on nivolumab response in previously treated patients with non-small cell lung cancer
  publication-title: J Thorac Oncol
– reference: Merritt CR, Ong GT, Church S, Barker K, Geiss G, Hoang M, et al. High multiplex, digital spatial profiling of proteins and RNA in fixed tissue using genomic detection methods. bioRxiv. 2019.
– volume: 12
  start-page: 208
  year: 2017
  ident: bib14
  article-title: PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project
  publication-title: J Thorac Oncol
– volume: 23
  start-page: 3585
  year: 2017
  ident: bib13
  article-title: Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer
  publication-title: Clin Cancer Res
– reference: .
– volume: 35
  start-page: 3924
  year: 2017
  ident: bib3
  article-title: Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057)
  publication-title: J Clin Oncol
– volume: 7
  year: 2017
  ident: bib20
  article-title: QuPath: open source software for digital pathology image analysis
  publication-title: Sci Rep.
– volume: 71
  start-page: 1078
  year: 2018
  ident: bib8
  article-title: A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8 and 22C3 in lung cancer and other malignancies
  publication-title: J Clin Pathol
– volume: 13
  start-page: 1302
  year: 2018
  ident: bib16
  article-title: PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project
  publication-title: J Thorac Oncol
– volume: 30
  start-page: 1411
  year: 2017
  ident: bib17
  article-title: PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability
  publication-title: Mod Pathol.
– volume: 31
  start-page: 623
  year: 2018
  ident: bib9
  article-title: Concordance study of PD-L1 expression in primary and metastatic bladder carcinomas: comparison of four commonly used antibodies and RNA expression
  publication-title: Mod Pathol.
– volume: 117
  start-page: 2192
  year: 2011
  end-page: 2201
  ident: bib7
  article-title: Overall survival and PD-L1 expression in metastasized malignant melanoma
  publication-title: Cancer.
– volume: 377
  start-page: 1919
  year: 2017
  ident: bib1
  article-title: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer
  publication-title: N Engl J Med
– volume: 387
  start-page: 1540
  year: 2016
  ident: bib2
  article-title: Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
  publication-title: Lancet.
– volume: 348
  start-page: 56
  year: 2015
  end-page: 61
  ident: bib21
  article-title: The future of immune checkpoint therapy
  publication-title: Science
– volume: 34
  start-page: 833
  year: 2016
  end-page: 42
  ident: CR4
  article-title: Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2015.63.7421
– volume: 7
  year: 2017
  ident: CR20
  article-title: QuPath: open source software for digital pathology image analysis
  publication-title: Sci Rep.
  doi: 10.1038/s41598-017-17204-5
– volume: 71
  start-page: 1078
  year: 2018
  end-page: 83.
  ident: CR8
  article-title: A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8 and 22C3 in lung cancer and other malignancies
  publication-title: J Clin Pathol
  doi: 10.1136/jclinpath-2018-205362
– ident: CR18
– volume: 387
  start-page: 1540
  year: 2016
  end-page: 50.
  ident: CR2
  article-title: Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
  publication-title: Lancet.
  doi: 10.1016/S0140-6736(15)01281-7
– volume: 25
  start-page: 5503
  year: 2019
  end-page: 12.
  ident: CR19
  article-title: High-plex predictive marker discovery for melanoma immunotherapy-treated patients using digital spatial profiling
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-19-0104
– volume: 30
  start-page: 1411
  year: 2017
  end-page: 21.
  ident: CR17
  article-title: PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability
  publication-title: Mod Pathol.
  doi: 10.1038/modpathol.2017.59
– volume: 31
  start-page: 623
  year: 2018
  end-page: 32.
  ident: CR9
  article-title: Concordance study of PD-L1 expression in primary and metastatic bladder carcinomas: comparison of four commonly used antibodies and RNA expression
  publication-title: Mod Pathol.
  doi: 10.1038/modpathol.2017.188
– volume: 14
  start-page: 847
  year: 2015
  end-page: 56
  ident: CR5
  article-title: PD-L1 expression as a predictive biomarker in cancer immunotherapy
  publication-title: Mol Cancer Ther
  doi: 10.1158/1535-7163.MCT-14-0983
– volume: 366
  start-page: 2455
  year: 2012
  end-page: 65
  ident: CR6
  article-title: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1200694
– volume: 117
  start-page: 2192
  year: 2011
  end-page: 201
  ident: CR7
  article-title: Overall survival and PD-L1 expression in metastasized malignant melanoma
  publication-title: Cancer.
  doi: 10.1002/cncr.25747
– volume: 13
  start-page: 367
  year: 2018
  end-page: 76.
  ident: CR11
  article-title: Comparison of four PD-L1 immunohistochemical assays in lung cancer
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2017.11.112
– volume: 12
  start-page: 208
  year: 2017
  end-page: 22.
  ident: CR14
  article-title: PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2016.11.2228
– volume: 23
  start-page: 3585
  year: 2017
  end-page: 91.
  ident: CR13
  article-title: Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-16-2375
– volume: 13
  start-page: 1302
  year: 2018
  end-page: 11.
  ident: CR16
  article-title: PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2018.05.013
– volume: 377
  start-page: 1919
  year: 2017
  end-page: 29.
  ident: CR1
  article-title: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1709937
– volume: 35
  start-page: 3924
  year: 2017
  end-page: 33.
  ident: CR3
  article-title: Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057)
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2017.74.3062
– volume: 3
  start-page: 1051
  year: 2017
  end-page: 8
  ident: CR12
  article-title: A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2017.0013
– volume: 348
  start-page: 56
  year: 2015
  end-page: 61
  ident: CR21
  article-title: The future of immune checkpoint therapy
  publication-title: Science
  doi: 10.1126/science.aaa8172
– volume: 13
  start-page: 377
  year: 2018
  end-page: 86.
  ident: CR10
  article-title: Predictive performance of four programmed cell death ligand 1 assay systems on nivolumab response in previously treated patients with non-small cell lung cancer
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2017.11.123
– volume: 3
  start-page: 256
  year: 2017
  end-page: 9.
  ident: CR15
  article-title: A quantitative comparison of antibodies to programmed cell death 1 ligand 1
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2016.3015
– ident: 10.1038/s41374-020-0424-5_bib18
  doi: 10.1101/559021
– volume: 387
  start-page: 1540
  year: 2016
  ident: 10.1038/s41374-020-0424-5_bib2
  article-title: Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
  publication-title: Lancet.
  doi: 10.1016/S0140-6736(15)01281-7
– volume: 13
  start-page: 377
  year: 2018
  ident: 10.1038/s41374-020-0424-5_bib10
  article-title: Predictive performance of four programmed cell death ligand 1 assay systems on nivolumab response in previously treated patients with non-small cell lung cancer
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2017.11.123
– volume: 3
  start-page: 256
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib15
  article-title: A quantitative comparison of antibodies to programmed cell death 1 ligand 1
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2016.3015
– volume: 7
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib20
  article-title: QuPath: open source software for digital pathology image analysis
  publication-title: Sci Rep.
  doi: 10.1038/s41598-017-17204-5
– volume: 34
  start-page: 833
  year: 2016
  ident: 10.1038/s41374-020-0424-5_bib4
  article-title: Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2015.63.7421
– volume: 12
  start-page: 208
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib14
  article-title: PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2016.11.2228
– volume: 35
  start-page: 3924
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib3
  article-title: Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057)
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2017.74.3062
– volume: 13
  start-page: 1302
  year: 2018
  ident: 10.1038/s41374-020-0424-5_bib16
  article-title: PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2018.05.013
– volume: 377
  start-page: 1919
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib1
  article-title: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1709937
– volume: 71
  start-page: 1078
  year: 2018
  ident: 10.1038/s41374-020-0424-5_bib8
  article-title: A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8 and 22C3 in lung cancer and other malignancies
  publication-title: J Clin Pathol
  doi: 10.1136/jclinpath-2018-205362
– volume: 14
  start-page: 847
  year: 2015
  ident: 10.1038/s41374-020-0424-5_bib5
  article-title: PD-L1 expression as a predictive biomarker in cancer immunotherapy
  publication-title: Mol Cancer Ther
  doi: 10.1158/1535-7163.MCT-14-0983
– volume: 348
  start-page: 56
  year: 2015
  ident: 10.1038/s41374-020-0424-5_bib21
  article-title: The future of immune checkpoint therapy
  publication-title: Science
  doi: 10.1126/science.aaa8172
– volume: 3
  start-page: 1051
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib12
  article-title: A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer
  publication-title: JAMA Oncol
  doi: 10.1001/jamaoncol.2017.0013
– volume: 366
  start-page: 2455
  year: 2012
  ident: 10.1038/s41374-020-0424-5_bib6
  article-title: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1200694
– volume: 25
  start-page: 5503
  year: 2019
  ident: 10.1038/s41374-020-0424-5_bib19
  article-title: High-plex predictive marker discovery for melanoma immunotherapy-treated patients using digital spatial profiling
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-19-0104
– volume: 117
  start-page: 2192
  year: 2011
  ident: 10.1038/s41374-020-0424-5_bib7
  article-title: Overall survival and PD-L1 expression in metastasized malignant melanoma
  publication-title: Cancer.
  doi: 10.1002/cncr.25747
– volume: 31
  start-page: 623
  year: 2018
  ident: 10.1038/s41374-020-0424-5_bib9
  article-title: Concordance study of PD-L1 expression in primary and metastatic bladder carcinomas: comparison of four commonly used antibodies and RNA expression
  publication-title: Mod Pathol.
  doi: 10.1038/modpathol.2017.188
– volume: 30
  start-page: 1411
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib17
  article-title: PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability
  publication-title: Mod Pathol.
  doi: 10.1038/modpathol.2017.59
– volume: 13
  start-page: 367
  year: 2018
  ident: 10.1038/s41374-020-0424-5_bib11
  article-title: Comparison of four PD-L1 immunohistochemical assays in lung cancer
  publication-title: J Thorac Oncol
  doi: 10.1016/j.jtho.2017.11.112
– volume: 23
  start-page: 3585
  year: 2017
  ident: 10.1038/s41374-020-0424-5_bib13
  article-title: Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-16-2375
SSID ssj0014465
Score 2.4638069
Snippet The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
elsevier
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 1311
SubjectTerms 13/105
13/51
631/61/32
692/53/2423
82/1
82/80
Antibodies
Apoptosis
Assaying
B7-H1 Antigen - analysis
B7-H1 Antigen - metabolism
Biomarkers - analysis
Biomarkers - metabolism
Biotechnology
Cell Line
Correlation analysis
Diagnostic systems
FDA approval
Fluorescence
Humans
Immune checkpoint
Immune system
Immunofluorescence
Immunohistochemistry
Immunohistochemistry - methods
Immunohistochemistry - statistics & numerical data
Immunotherapy
L1 protein
Laboratory Medicine
Medicine
Medicine & Public Health
New technology
Pathology
PD-1 protein
PD-L1 protein
Protein Array Analysis - methods
Protein Array Analysis - statistics & numerical data
Proteins
Reproducibility of Results
Standardization
Tissue Array Analysis - methods
Tissue Array Analysis - statistics & numerical data
Tissues
Tumor cells
Title Digital quantitative assessment of PD-L1 using digital spatial profiling
URI https://dx.doi.org/10.1038/s41374-020-0424-5
https://link.springer.com/article/10.1038/s41374-020-0424-5
https://www.ncbi.nlm.nih.gov/pubmed/32249818
https://www.proquest.com/docview/2474990922
https://www.proquest.com/docview/2386450104
https://pubmed.ncbi.nlm.nih.gov/PMC7502436
Volume 100
WOSCitedRecordID wos000523949500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVPQU
  databaseName: Biological Science Database
  customDbUrl:
  eissn: 1530-0307
  dateEnd: 20221231
  omitProxy: false
  ssIdentifier: ssj0014465
  issn: 0023-6837
  databaseCode: M7P
  dateStart: 20000101
  isFulltext: true
  titleUrlDefault: http://search.proquest.com/biologicalscijournals
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Health & Medical Collection
  customDbUrl:
  eissn: 1530-0307
  dateEnd: 20221231
  omitProxy: false
  ssIdentifier: ssj0014465
  issn: 0023-6837
  databaseCode: 7X7
  dateStart: 20000101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/healthcomplete
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Central
  customDbUrl:
  eissn: 1530-0307
  dateEnd: 20221231
  omitProxy: false
  ssIdentifier: ssj0014465
  issn: 0023-6837
  databaseCode: BENPR
  dateStart: 20000101
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Public Health Database
  customDbUrl:
  eissn: 1530-0307
  dateEnd: 20221231
  omitProxy: false
  ssIdentifier: ssj0014465
  issn: 0023-6837
  databaseCode: 8C1
  dateStart: 20000101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/publichealth
  providerName: ProQuest
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1La9wwEB7apJRc-m7iNl1c6KnFxHrYsk6lzYMc2mUpLexNyLKULgRvEu_m92ckyw5pyF56scEagcQ8NKMZzwfwiWgubF6gphGBAYoxaAdlXWS5lUbqhllrXQCbENNpNZ_LWbxw62JZ5WATg6FulsbfkR9QLtA5zyWlXy8uM48a5bOrEULjMWx72Gwv52I-BlyhGVhf4sGyEiOxIavJqoMOjbfgmQ-efPIvKx46l-77nffLJ__JoYaj6eT5_27qBTyLTmn6rZeil_DItq_g6c-Ydn8Np0eLMw8ukl6udRv-SkMbmeqxqWe6dOnsKPtBUl9Gf5Y2kbzz5dr47oHBceQN_Dk5_n14mkUIhsygY7bKiLOllcQQoYUVrqFCU99Csa6oZg6_06YUpTOmIY7RwjVoOgsiKoZRVllzyd7CVrts7R6kzDBSOi1cbjWvCyZrJzHYs7w2ed5ULIF8YIAysT-5h8k4VyFPzirV80whz5TnmSoS-DxOueibc2wi5gNXVfQueq9B4eGxadr-wDoV1btTt3xL4OM4jIrpsy26tcs10rCq5IUPdxPY7QVmXCRaUS7RVUpA3BGlkcA3_b470i7-hubf6OFRzsoEvgxCd7usBzfxbvMm3sMO9ZoQahT3YWt1tbYf4Im5Xi26q0nQqfCs8Fkdkglsfz-ezn5NfKHs7AbfvSnM
linkProvider ProQuest
linkToHtml http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB5VBQEX3tBAASPBBWQ1sZ04OSCEulRbdbvqoUi9Gcexy0pVtm12QfwpfiNj51GVqnvrgVOkeCzZ8TevzHgG4F2ihbRxipyWSHRQjEE5WJQpjW1hCl1xa60LzSbkdJofHRUHa_Cnvwvj0yp7mRgEdTU3_h_5FhMSjfO4YOzz6Rn1XaN8dLVvodHCYs_-_oUuW_Npd4Tn-56xna-H22PadRWgBm2NBU2czWyRmERqaaWrmNTMVwUsc6a5w_esymTmjKkSx1nqKpQGaSJzjo5DVgpffAlF_i3BGfdclG8PKSWh-FibUsJphp5fH0Xl-VaDykIK6p01H2yk6XV68KqdezVd85-YbVCFOw_-t4_4EO53Rjf50nLJI1iz9WO4s9-lFTyB8Wh27JunkLOlrsOtO9QBRA9FS8nckYMRnSTEXxM4JlVH3vh0dHy2jc9x5Cl8u5F9PIP1el7bDSDc8CRzWrrYalGmvChdgc6sFaWJ4yrnEcT9gSvT1V_3bUBOVMgD4LlqMaIQI8pjRKURfBimnLbFR1YRix5FqrOeWqtIoXJcNW2zh4rqxFejLnASwdthGAWPjybp2s6XSMPzTKTenY_geQvQYZGoJUSBpmAE8hJ0BwJf1PzySD37EYqbowXLBM8i-NiD_GJZ127ixepNvIG748P9iZrsTvdewj3muTDkY27C-uJ8aV_BbfNzMWvOXwd-JvD9prH_F0IngLk
linkToPdf http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB5VW1Rx4U0JFAgSXEDWJrYTJwdUFbarVi2rFQKpN-M4dlkJZdtmF8Rf66_rOHFSlap764FTpHgs2fE3r8x4BuBtrLgwUYKcFgt0ULRGOZgXCYlMrnNVMmOMbZpNiMkkOzrKp2tw3t2FcWmVnUxsBHU51-4f-ZBygcZ5lFM6tD4tYjoab5-cEtdBykVau3YaLUQOzN8_6L7VH_dHeNbvKB3vfvu8R3yHAaLR7liQ2JrU5LGOhRJG2JIKRV2FwCKjill8T8tUpFbrMraMJrZEyZDEImPoRKQFd4WYUPyvC4ZOzwDWP-1Opl_7GIYrRdYmmDCSoh_YxVRZNqxRdQhOnOvmQo8kuUkrXrd6rydv_hPBbRTj-P7__EkfwD1vjoc7Lf88hDVTPYKNLz7h4DHsjWbHrq1KeLpUVXMfD7VDqPpypuHchtMROYxDd4HgOCw9ee0S1fHZtkTHkSfw_Vb28RQG1bwyzyBkmsWpVcJGRvEiYXlhc3RzDS90FJUZCyDqDl9qX5ndNQj5JZsMAZbJFi8S8SIdXmQSwPt-yklblmQVMe8QJb1d1dpLEtXmqmlbHWykF2y1vMRMAG_6YRRJLs6kKjNfIg3LUp44Rz-AzRas_SJRf_AcjcQAxBUY9wSu3PnVkWr2syl7jrYt5SwN4EMH-Mtl3biJ56s38Ro2EPLycH9y8ALuUseQTaLmFgwWZ0vzEu7o34tZffbKM3cIP24b_BfK-YsX
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Digital+quantitative+assessment+of+PD-L1+using+digital+spatial+profiling&rft.jtitle=Laboratory+investigation&rft.au=Gupta%2C+Swati&rft.au=Zugazagoitia%2C+Jon&rft.au=Martinez-Morilla%2C+Sandra&rft.au=Fuhrman%2C+Kit&rft.date=2020-10-01&rft.issn=1530-0307&rft.eissn=1530-0307&rft.volume=100&rft.issue=10&rft.spage=1311&rft_id=info:doi/10.1038%2Fs41374-020-0424-5&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0023-6837&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0023-6837&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0023-6837&client=summon