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Resistance to systemic immune checkpoint inhibition in the peritoneal niche

Immune checkpoint inhibition (ICI) is an established therapeutic option for patients with deficient mismatch repair or high levels of microsatellite instability tumors. Yet, response to ICI among this group is varied, with nearly one-third of patients exhibiting primary resistance. Initial efforts i...

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Autores principales: Chia, Daryl Kai Ann, Gwee, Yong Xiang, Sundar, Raghav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214396/
https://www.ncbi.nlm.nih.gov/pubmed/35728873
http://dx.doi.org/10.1136/jitc-2022-004749
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author Chia, Daryl Kai Ann
Gwee, Yong Xiang
Sundar, Raghav
author_facet Chia, Daryl Kai Ann
Gwee, Yong Xiang
Sundar, Raghav
author_sort Chia, Daryl Kai Ann
collection PubMed
description Immune checkpoint inhibition (ICI) is an established therapeutic option for patients with deficient mismatch repair or high levels of microsatellite instability tumors. Yet, response to ICI among this group is varied, with nearly one-third of patients exhibiting primary resistance. Initial efforts in studying mechanisms of resistance to ICI have focused on intrinsic tumor factors. Host factors such as metastatic niches have unique biological properties that may mediate resistance to ICI but have been less studied date. Patients with metastatic d-MMR/MSI-H gastrointestinal cancers and peritoneal metastases (PM) who had concurrent ascites have been recently shown to have worse outcomes with ICI therapy compared with patients with PM without ascites and patients with non-PM metastases. The juxtaposition of tumors with an intrinsic sensitivity to ICI failing to respond by virtue of the presence of ascites within the peritoneum, brings to the forefront the critical role of the metastatic niche. In this commentary, we discuss mechanisms for ICI resistance that may arise from the immunoprivileged state of the peritoneal cavity, paracrine factors within malignant ascites or tumor-peritoneum interactions. An improved understanding of the peritoneal microenvironment and the use of peritoneal-directed therapies may ameliorate the modest benefit of ICIs in this unique clinical entity.
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spelling pubmed-92143962022-07-07 Resistance to systemic immune checkpoint inhibition in the peritoneal niche Chia, Daryl Kai Ann Gwee, Yong Xiang Sundar, Raghav J Immunother Cancer Commentary Immune checkpoint inhibition (ICI) is an established therapeutic option for patients with deficient mismatch repair or high levels of microsatellite instability tumors. Yet, response to ICI among this group is varied, with nearly one-third of patients exhibiting primary resistance. Initial efforts in studying mechanisms of resistance to ICI have focused on intrinsic tumor factors. Host factors such as metastatic niches have unique biological properties that may mediate resistance to ICI but have been less studied date. Patients with metastatic d-MMR/MSI-H gastrointestinal cancers and peritoneal metastases (PM) who had concurrent ascites have been recently shown to have worse outcomes with ICI therapy compared with patients with PM without ascites and patients with non-PM metastases. The juxtaposition of tumors with an intrinsic sensitivity to ICI failing to respond by virtue of the presence of ascites within the peritoneum, brings to the forefront the critical role of the metastatic niche. In this commentary, we discuss mechanisms for ICI resistance that may arise from the immunoprivileged state of the peritoneal cavity, paracrine factors within malignant ascites or tumor-peritoneum interactions. An improved understanding of the peritoneal microenvironment and the use of peritoneal-directed therapies may ameliorate the modest benefit of ICIs in this unique clinical entity. BMJ Publishing Group 2022-06-21 /pmc/articles/PMC9214396/ /pubmed/35728873 http://dx.doi.org/10.1136/jitc-2022-004749 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
spellingShingle Commentary
Chia, Daryl Kai Ann
Gwee, Yong Xiang
Sundar, Raghav
Resistance to systemic immune checkpoint inhibition in the peritoneal niche
title Resistance to systemic immune checkpoint inhibition in the peritoneal niche
title_full Resistance to systemic immune checkpoint inhibition in the peritoneal niche
title_fullStr Resistance to systemic immune checkpoint inhibition in the peritoneal niche
title_full_unstemmed Resistance to systemic immune checkpoint inhibition in the peritoneal niche
title_short Resistance to systemic immune checkpoint inhibition in the peritoneal niche
title_sort resistance to systemic immune checkpoint inhibition in the peritoneal niche
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214396/
https://www.ncbi.nlm.nih.gov/pubmed/35728873
http://dx.doi.org/10.1136/jitc-2022-004749
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