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PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer

SIMPLE SUMMARY: Over the last decade, immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) have dramatically changed the therapeutic algorithm of several hematological and solid tumors. Of note, thes...

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Autores principales: Rizzo, Alessandro, Ricci, Angela Dalia, Brandi, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867133/
https://www.ncbi.nlm.nih.gov/pubmed/33535621
http://dx.doi.org/10.3390/cancers13030558
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author Rizzo, Alessandro
Ricci, Angela Dalia
Brandi, Giovanni
author_facet Rizzo, Alessandro
Ricci, Angela Dalia
Brandi, Giovanni
author_sort Rizzo, Alessandro
collection PubMed
description SIMPLE SUMMARY: Over the last decade, immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) have dramatically changed the therapeutic algorithm of several hematological and solid tumors. Of note, these agents have been also investigated in biliary tract cancer (BTC), reporting controversial results so far; in this setting, the role of ICIs is still to be established, and available data on immunotherapy in BTC patients are mainly limited to sub-analyses of basket trials and small single-arm studies. A crucial challenge is represented by the lack of validated predictive biomarkers, that could help identify responders to immunotherapy, a high unmet need in these immunologically “cold” malignancies where ICIs are still looking for their niche. ABSTRACT: Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers.
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spelling pubmed-78671332021-02-07 PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer Rizzo, Alessandro Ricci, Angela Dalia Brandi, Giovanni Cancers (Basel) Review SIMPLE SUMMARY: Over the last decade, immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) have dramatically changed the therapeutic algorithm of several hematological and solid tumors. Of note, these agents have been also investigated in biliary tract cancer (BTC), reporting controversial results so far; in this setting, the role of ICIs is still to be established, and available data on immunotherapy in BTC patients are mainly limited to sub-analyses of basket trials and small single-arm studies. A crucial challenge is represented by the lack of validated predictive biomarkers, that could help identify responders to immunotherapy, a high unmet need in these immunologically “cold” malignancies where ICIs are still looking for their niche. ABSTRACT: Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers. MDPI 2021-02-01 /pmc/articles/PMC7867133/ /pubmed/33535621 http://dx.doi.org/10.3390/cancers13030558 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rizzo, Alessandro
Ricci, Angela Dalia
Brandi, Giovanni
PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
title PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
title_full PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
title_fullStr PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
title_full_unstemmed PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
title_short PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
title_sort pd-l1, tmb, msi, and other predictors of response to immune checkpoint inhibitors in biliary tract cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867133/
https://www.ncbi.nlm.nih.gov/pubmed/33535621
http://dx.doi.org/10.3390/cancers13030558
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