Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC)
The emergence of immunotherapy has dramatically changed how non–small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and s...
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| Veröffentlicht in: | Cancer Jg. 126; H. 2; S. 260 - 270 |
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| Hauptverfasser: | , , |
| Format: | Journal Article |
| Sprache: | Englisch |
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United States
Wiley Subscription Services, Inc
15.01.2020
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| ISSN: | 0008-543X, 1097-0142, 1097-0142 |
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| Abstract | The emergence of immunotherapy has dramatically changed how non–small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD‐L1) expression is the current standard. The extent of PD‐L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD‐L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor‐infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD‐L1 as well as other emerging and investigational tissue‐based and serum‐based markers that have potential to better predict responders to immunotherapy.
Immunotherapy has dramatically changed how advanced non–small cell lung cancer is treated, and longer survival is now possible for some patients, although not all patients benefit from these agents, and some suffer toxicities, highlighting the importance of biomarkers that predict efficacy. This article reviews several biomarkers, including programmed death ligand 1, as well as other emerging and investigational tissue‐based and serum‐based markers that have potential to better predict responders to checkpoint inhibition. |
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| AbstractList | The emergence of immunotherapy has dramatically changed how non–small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD‐L1) expression is the current standard. The extent of PD‐L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD‐L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor‐infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD‐L1 as well as other emerging and investigational tissue‐based and serum‐based markers that have potential to better predict responders to immunotherapy.
Immunotherapy has dramatically changed how advanced non–small cell lung cancer is treated, and longer survival is now possible for some patients, although not all patients benefit from these agents, and some suffer toxicities, highlighting the importance of biomarkers that predict efficacy. This article reviews several biomarkers, including programmed death ligand 1, as well as other emerging and investigational tissue‐based and serum‐based markers that have potential to better predict responders to checkpoint inhibition. The emergence of immunotherapy has dramatically changed how non–small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD‐L1) expression is the current standard. The extent of PD‐L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD‐L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor‐infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD‐L1 as well as other emerging and investigational tissue‐based and serum‐based markers that have potential to better predict responders to immunotherapy. The emergence of immunotherapy has dramatically changed how NSCLC is treated and longer survival is now possible for some patients, even those with advanced disease. While some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor PD-L1 expression is the current standard. Extent of PD-L1 expression via immunohistochemisty (IHC) has demonstrated correlation with treatment response, though limitations with this marker exist. Recently, tumor mutational burden (TMB) has emerged as an alternative biomarker and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor. Gene expression signatures, tumor genotype, such as the presence of an oncogenic driver mutation, as well as density of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied and some have demonstrated to be predictive, though most are still investigational and need prospective validation. This paper reviews the biomarker PD-L1, as well as other emerging and investigational tissue-based and serum-based markers that have potential to better predict responders to immunotherapy. Immunotherapy has dramatically changed how advanced NSCLC is treated and longer survival is now possible for some patients. However, not all patients benefit from these agents and some suffer toxicities, highlighting the importance of biomarkers that predict efficacy. This article reviews several biomarkers including PD-L1, as well as other emerging and investigational tissue and serum-based markers that have potential to better predict responders to checkpoint inhibition. The emergence of immunotherapy has dramatically changed how non-small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD-L1) expression is the current standard. The extent of PD-L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor-infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD-L1 as well as other emerging and investigational tissue-based and serum-based markers that have potential to better predict responders to immunotherapy.The emergence of immunotherapy has dramatically changed how non-small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD-L1) expression is the current standard. The extent of PD-L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor-infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD-L1 as well as other emerging and investigational tissue-based and serum-based markers that have potential to better predict responders to immunotherapy. |
| Author | Boumber, Yanis Borghaei, Hossein Bodor, J. Nicholas |
| AuthorAffiliation | 1 Department of Hematology / Oncology, Fox Chase Cancer Center, Philadelphia, PA 3 Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2 Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA |
| AuthorAffiliation_xml | – name: 3 Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia – name: 1 Department of Hematology / Oncology, Fox Chase Cancer Center, Philadelphia, PA – name: 2 Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA |
| Author_xml | – sequence: 1 givenname: J. Nicholas surname: Bodor fullname: Bodor, J. Nicholas organization: Fox Chase Cancer Center – sequence: 2 givenname: Yanis surname: Boumber fullname: Boumber, Yanis organization: Kazan Federal University – sequence: 3 givenname: Hossein orcidid: 0000-0002-2577-4454 surname: Borghaei fullname: Borghaei, Hossein email: hossein.borghaei@fccc.edu organization: Fox Chase Cancer Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31691957$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | 2019 American Cancer Society 2019 American Cancer Society. 2020 American Cancer Society |
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| ISSN | 0008-543X 1097-0142 |
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| Keywords | programmed death ligand 1 (PD-L1) tumor mutational burden (TMB) biomarkers immunotherapy non-small-cell lung cancer |
| Language | English |
| License | 2019 American Cancer Society. |
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| PublicationDate | January 15, 2020 |
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| PublicationTitle | Cancer |
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| SubjectTerms | Antineoplastic Agents, Immunological - pharmacology Antineoplastic Agents, Immunological - therapeutic use Apoptosis B7-H1 Antigen - antagonists & inhibitors B7-H1 Antigen - genetics B7-H1 Antigen - immunology B7-H1 Antigen - metabolism Biomarkers Biomarkers, Tumor - analysis Biomarkers, Tumor - genetics Carcinoma, Non-Small-Cell Lung - blood Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - immunology Drug Monitoring - methods Gene expression Gene Expression Profiling Genotypes Humans Immune checkpoint inhibitors Immunohistochemistry Immunotherapy Liquid Biopsy - methods Lung - drug effects Lung - immunology Lung - pathology Lung cancer Lung Neoplasms - blood Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - immunology Lymphocytes Mutation Mutation Rate Non-small cell lung carcinoma non–small‐cell lung cancer Oncology PD-L1 protein programmed death ligand 1 (PD‐L1) Small cell lung carcinoma Treatment Outcome Tumor Microenvironment - drug effects Tumor Microenvironment - immunology tumor mutational burden (TMB) Tumors |
| Title | Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC) |
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