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Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates
Despite the recent successes and durable responses with immune checkpoint inhibitors (ICI), many cancer patients, including those with melanoma, do not derive long-term benefits from ICI therapies. The lack of predictive biomarkers to stratify patients to targeted treatments has been the driver of p...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820306/ https://www.ncbi.nlm.nih.gov/pubmed/36613491 http://dx.doi.org/10.3390/ijms24010041 |
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author | Seyhan, Attila A. Carini, Claudio |
author_facet | Seyhan, Attila A. Carini, Claudio |
author_sort | Seyhan, Attila A. |
collection | PubMed |
description | Despite the recent successes and durable responses with immune checkpoint inhibitors (ICI), many cancer patients, including those with melanoma, do not derive long-term benefits from ICI therapies. The lack of predictive biomarkers to stratify patients to targeted treatments has been the driver of primary treatment failure and represents an unmet medical need in melanoma and other cancers. Understanding genomic correlations with response and resistance to ICI will enhance cancer patients’ benefits. Building on insights into interplay with the complex tumor microenvironment (TME), the ultimate goal should be assessing how the tumor ’instructs’ the local immune system to create its privileged niche with a focus on genomic reprogramming within the TME. It is hypothesized that this genomic reprogramming determines the response to ICI. Furthermore, emerging genomic signatures of ICI response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways, are gaining momentum. In addition, emerging data suggest a role for checkpoint regulators, T cell functionality, chromatin modifiers, and copy-number alterations in mediating the selective response to ICI. As such, efforts to contextualize genomic correlations with response into a more insightful understanding of tumor immune biology will help the development of novel biomarkers and therapeutic strategies to overcome ICI resistance. |
format | Online Article Text |
id | pubmed-9820306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98203062023-01-07 Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates Seyhan, Attila A. Carini, Claudio Int J Mol Sci Review Despite the recent successes and durable responses with immune checkpoint inhibitors (ICI), many cancer patients, including those with melanoma, do not derive long-term benefits from ICI therapies. The lack of predictive biomarkers to stratify patients to targeted treatments has been the driver of primary treatment failure and represents an unmet medical need in melanoma and other cancers. Understanding genomic correlations with response and resistance to ICI will enhance cancer patients’ benefits. Building on insights into interplay with the complex tumor microenvironment (TME), the ultimate goal should be assessing how the tumor ’instructs’ the local immune system to create its privileged niche with a focus on genomic reprogramming within the TME. It is hypothesized that this genomic reprogramming determines the response to ICI. Furthermore, emerging genomic signatures of ICI response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways, are gaining momentum. In addition, emerging data suggest a role for checkpoint regulators, T cell functionality, chromatin modifiers, and copy-number alterations in mediating the selective response to ICI. As such, efforts to contextualize genomic correlations with response into a more insightful understanding of tumor immune biology will help the development of novel biomarkers and therapeutic strategies to overcome ICI resistance. MDPI 2022-12-20 /pmc/articles/PMC9820306/ /pubmed/36613491 http://dx.doi.org/10.3390/ijms24010041 Text en © 2022 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 Seyhan, Attila A. Carini, Claudio Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates |
title | Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates |
title_full | Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates |
title_fullStr | Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates |
title_full_unstemmed | Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates |
title_short | Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates |
title_sort | insights and strategies of melanoma immunotherapy: predictive biomarkers of response and resistance and strategies to improve response rates |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820306/ https://www.ncbi.nlm.nih.gov/pubmed/36613491 http://dx.doi.org/10.3390/ijms24010041 |
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