Cargando…

Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events

SIMPLE SUMMARY: Immune-checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer, but they cause immune-related adverse events (irAEs) in around 40% of patients treated. Identifying biomarkers predictive of irAEs has become a priority for the optimal management of patients on ICI...

Descripción completa

Detalles Bibliográficos
Autores principales: Les, Iñigo, Martínez, Mireia, Pérez-Francisco, Inés, Cabero, María, Teijeira, Lucía, Arrazubi, Virginia, Torrego, Nuria, Campillo-Calatayud, Ana, Elejalde, Iñaki, Kochan, Grazyna, Escors, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000735/
https://www.ncbi.nlm.nih.gov/pubmed/36900420
http://dx.doi.org/10.3390/cancers15051629
_version_ 1784903953082744832
author Les, Iñigo
Martínez, Mireia
Pérez-Francisco, Inés
Cabero, María
Teijeira, Lucía
Arrazubi, Virginia
Torrego, Nuria
Campillo-Calatayud, Ana
Elejalde, Iñaki
Kochan, Grazyna
Escors, David
author_facet Les, Iñigo
Martínez, Mireia
Pérez-Francisco, Inés
Cabero, María
Teijeira, Lucía
Arrazubi, Virginia
Torrego, Nuria
Campillo-Calatayud, Ana
Elejalde, Iñaki
Kochan, Grazyna
Escors, David
author_sort Les, Iñigo
collection PubMed
description SIMPLE SUMMARY: Immune-checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer, but they cause immune-related adverse events (irAEs) in around 40% of patients treated. Identifying biomarkers predictive of irAEs has become a priority for the optimal management of patients on ICIs. Herein, we review the state of the art regarding the most relevant biomarkers for predicting irAEs, distinguishing between biomarkers already clinically available and those under investigation. Although none of these biomarkers has been validated in prospective studies, there is growing evidence supporting their use for irAE prediction and clinical characterization, which depend on cancer type, ICI agent and organ affected by the toxicity. A better understanding of the pathogenic mechanisms underlying irAEs and the combination of different emerging biomarkers would allow us to improve the risk-benefit balance for patients who are candidates for ICI therapy. ABSTRACT: Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation and antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With the approval of more ICIs, irAE prediction has become a key factor in improving patient survival and quality of life. Several biomarkers have been described as potential irAE predictors, some of them are already available for clinical use and others are under development; examples include circulating blood cell counts and ratios, T-cell expansion and diversification, cytokines, autoantibodies and autoantigens, serum and other biological fluid proteins, human leucocyte antigen genotypes, genetic variations and gene profiles, microRNAs, and the gastrointestinal microbiome. Nevertheless, it is difficult to generalize the application of irAE biomarkers based on the current evidence because most studies have been retrospective, time-limited and restricted to a specific type of cancer, irAE or ICI. Long-term prospective cohorts and real-life studies are needed to assess the predictive capacity of different potential irAE biomarkers, regardless of the ICI type, organ involved or cancer site.
format Online
Article
Text
id pubmed-10000735
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100007352023-03-11 Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events Les, Iñigo Martínez, Mireia Pérez-Francisco, Inés Cabero, María Teijeira, Lucía Arrazubi, Virginia Torrego, Nuria Campillo-Calatayud, Ana Elejalde, Iñaki Kochan, Grazyna Escors, David Cancers (Basel) Review SIMPLE SUMMARY: Immune-checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer, but they cause immune-related adverse events (irAEs) in around 40% of patients treated. Identifying biomarkers predictive of irAEs has become a priority for the optimal management of patients on ICIs. Herein, we review the state of the art regarding the most relevant biomarkers for predicting irAEs, distinguishing between biomarkers already clinically available and those under investigation. Although none of these biomarkers has been validated in prospective studies, there is growing evidence supporting their use for irAE prediction and clinical characterization, which depend on cancer type, ICI agent and organ affected by the toxicity. A better understanding of the pathogenic mechanisms underlying irAEs and the combination of different emerging biomarkers would allow us to improve the risk-benefit balance for patients who are candidates for ICI therapy. ABSTRACT: Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation and antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With the approval of more ICIs, irAE prediction has become a key factor in improving patient survival and quality of life. Several biomarkers have been described as potential irAE predictors, some of them are already available for clinical use and others are under development; examples include circulating blood cell counts and ratios, T-cell expansion and diversification, cytokines, autoantibodies and autoantigens, serum and other biological fluid proteins, human leucocyte antigen genotypes, genetic variations and gene profiles, microRNAs, and the gastrointestinal microbiome. Nevertheless, it is difficult to generalize the application of irAE biomarkers based on the current evidence because most studies have been retrospective, time-limited and restricted to a specific type of cancer, irAE or ICI. Long-term prospective cohorts and real-life studies are needed to assess the predictive capacity of different potential irAE biomarkers, regardless of the ICI type, organ involved or cancer site. MDPI 2023-03-06 /pmc/articles/PMC10000735/ /pubmed/36900420 http://dx.doi.org/10.3390/cancers15051629 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Les, Iñigo
Martínez, Mireia
Pérez-Francisco, Inés
Cabero, María
Teijeira, Lucía
Arrazubi, Virginia
Torrego, Nuria
Campillo-Calatayud, Ana
Elejalde, Iñaki
Kochan, Grazyna
Escors, David
Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
title Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
title_full Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
title_fullStr Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
title_full_unstemmed Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
title_short Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
title_sort predictive biomarkers for checkpoint inhibitor immune-related adverse events
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000735/
https://www.ncbi.nlm.nih.gov/pubmed/36900420
http://dx.doi.org/10.3390/cancers15051629
work_keys_str_mv AT lesinigo predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT martinezmireia predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT perezfranciscoines predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT caberomaria predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT teijeiralucia predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT arrazubivirginia predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT torregonuria predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT campillocalatayudana predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT elejaldeinaki predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT kochangrazyna predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents
AT escorsdavid predictivebiomarkersforcheckpointinhibitorimmunerelatedadverseevents