Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer
Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biolo...
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| Published in: | Journal of experimental & clinical cancer research Vol. 41; no. 1; pp. 186 - 14 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
BioMed Central
02.06.2022
BioMed Central Ltd Springer Nature B.V BMC |
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| ISSN: | 1756-9966, 0392-9078, 1756-9966 |
| Online Access: | Get full text |
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| Abstract | Background
Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs.
Methods
Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively.
Results
As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival.
Conclusion
These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. |
|---|---|
| AbstractList | Abstract Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs.BACKGROUNDImmune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs.Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively.METHODSDynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively.As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival.RESULTSAs a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival.These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.CONCLUSIONThese findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 [+ or -] 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. Keywords: Extracellular vesicles, PD-L1, Biomarkers, Immunotherapy, NSCLC Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 [+ or -] 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs. |
| ArticleNumber | 186 |
| Audience | Academic |
| Author | Ak, Murat Barron, Feliciano Manca, Paolo Gunasekaran, Muthukumar Lara-Mejia, Luis Hirsch, Fred R. Serrano, Maria Jose de Miguel-Perez, Diego Arrieta, Oscar Mamindla, Priyadarshini Adamo, Vincenzo Cooper, Brandon Naing, Aung Lapidus, Rena G. Colen, Rivka R. Rolfo, Christian Peterson, Christine B. Peddagangireddy, Vishal Cardona, Andres F. Kaushal, Sunjay Buemi, Francesco Hsia, Ru-Ching Mack, Philip C. Russo, Alessandro Er, Mehmet E. |
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Papardo & Department of Human Pathology, University of Messina – sequence: 3 givenname: Oscar surname: Arrieta fullname: Arrieta, Oscar organization: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan) – sequence: 4 givenname: Murat surname: Ak fullname: Ak, Murat organization: Department of Radiology, University of Pittsburgh, Hillman Cancer Center, University of Pittsburgh Medical Center – sequence: 5 givenname: Feliciano surname: Barron fullname: Barron, Feliciano organization: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan) – sequence: 6 givenname: Muthukumar surname: Gunasekaran fullname: Gunasekaran, Muthukumar organization: Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine – sequence: 7 givenname: Priyadarshini surname: Mamindla fullname: Mamindla, Priyadarshini organization: Hillman Cancer Center, University of Pittsburgh Medical Center – sequence: 8 givenname: Luis surname: Lara-Mejia fullname: Lara-Mejia, Luis organization: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan) – sequence: 9 givenname: Christine B. surname: Peterson fullname: Peterson, Christine B. organization: The University of Texas MD Anderson Cancer Center – sequence: 10 givenname: Mehmet E. surname: Er fullname: Er, Mehmet E. organization: Department of Radiology, University of Pittsburgh, Hillman Cancer Center, University of Pittsburgh Medical Center – sequence: 11 givenname: Vishal surname: Peddagangireddy fullname: Peddagangireddy, Vishal organization: Department of Radiology, University of Pittsburgh – sequence: 12 givenname: Francesco surname: Buemi fullname: Buemi, Francesco organization: Medical Oncology Unit, A.O. Papardo & Department of Human Pathology, University of Messina – sequence: 13 givenname: Brandon surname: Cooper fullname: Cooper, Brandon organization: Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine – sequence: 14 givenname: Paolo surname: Manca fullname: Manca, Paolo organization: Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano – sequence: 15 givenname: Rena G. surname: Lapidus fullname: Lapidus, Rena G. organization: Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine – sequence: 16 givenname: Ru-Ching surname: Hsia fullname: Hsia, Ru-Ching organization: Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine – sequence: 17 givenname: Andres F. surname: Cardona fullname: Cardona, Andres F. organization: Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC) / Foundation for Clinical and Applied Cancer Research (FICMAC) / Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad El Bosque – sequence: 18 givenname: Aung surname: Naing fullname: Naing, Aung organization: Departments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center – sequence: 19 givenname: Sunjay surname: Kaushal fullname: Kaushal, Sunjay organization: Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine – sequence: 20 givenname: Fred R. surname: Hirsch fullname: Hirsch, Fred R. organization: Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai – sequence: 21 givenname: Philip C. surname: Mack fullname: Mack, Philip C. organization: Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai – sequence: 22 givenname: Maria Jose surname: Serrano fullname: Serrano, Maria Jose organization: GENYO Centre for Genomics and Oncological Research, Pfizer/ University of Granada/ Andalusian Regional Government, PTS Granada – sequence: 23 givenname: Vincenzo surname: Adamo fullname: Adamo, Vincenzo organization: Medical Oncology Unit, A.O. Papardo & Department of Human Pathology, University of Messina – sequence: 24 givenname: Rivka R. surname: Colen fullname: Colen, Rivka R. organization: Department of Radiology, University of Pittsburgh, Hillman Cancer Center, University of Pittsburgh Medical Center – sequence: 25 givenname: Christian surname: Rolfo fullname: Rolfo, Christian email: christian.rolfo@mssm.edu organization: Center for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35650597$$D View this record in MEDLINE/PubMed |
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| DOI | 10.1186/s13046-022-02379-1 |
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| Keywords | Extracellular vesicles PD-L1 Biomarkers NSCLC Immunotherapy |
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| License | 2022. The Author(s). Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical... Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and... Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical... Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and... Abstract Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived... |
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| SubjectTerms | Apoptosis B7-H1 Antigen - metabolism Biomarkers Biomedical and Life Sciences Biomedicine Biopsy Cancer Research Cancer therapies Carcinoma, Non-Small-Cell Lung - pathology Development and progression Extracellular vesicles Extracellular Vesicles - metabolism Humans Immune checkpoint inhibitors Immune Checkpoint Inhibitors - therapeutic use Immune response Immunology Immunotherapy Lung cancer Lung cancer, Non-small cell Lung cancer, Small cell Lung Neoplasms Medical imaging Metastasis NSCLC Oncology Patient outcomes PD-L1 Performance evaluation Prognosis Prospective Studies Retrospective Studies Software Statistical analysis Tumors |
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| Title | Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer |
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