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Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma

Immune checkpoint blockade (ICB) has been explored as a therapeutic strategy to recover the antitumor immune activities against endometrial cancer (EC) escaping from immune surveillance. Increasing evidence has indicated that microsatellite instability (MSI) is a promising biomarker to stratify pati...

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Autores principales: Chen, Qiang, Wang, Chongyang, Lei, Xinyi, Huang, Ting, Zhou, Renyu, Lu, Yuanzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313908/
https://www.ncbi.nlm.nih.gov/pubmed/35898926
http://dx.doi.org/10.1155/2022/9060243
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author Chen, Qiang
Wang, Chongyang
Lei, Xinyi
Huang, Ting
Zhou, Renyu
Lu, Yuanzhi
author_facet Chen, Qiang
Wang, Chongyang
Lei, Xinyi
Huang, Ting
Zhou, Renyu
Lu, Yuanzhi
author_sort Chen, Qiang
collection PubMed
description Immune checkpoint blockade (ICB) has been explored as a therapeutic strategy to recover the antitumor immune activities against endometrial cancer (EC) escaping from immune surveillance. Increasing evidence has indicated that microsatellite instability (MSI) is a promising biomarker to stratify patients for the ICB therapy. However, even in patients with MSI-High (MSI-H) endometrial cancers, PD-L1 inhibitors, avelumab, and durvalumab have shown only 27% of response rates. Therefore, there is an urgent need to discover new biomarkers for a predictive response to ICB therapy. In this study, we demonstrated that the immune cytolytic activity (CYT) index was significantly correlated with the development and response to immunotherapy in EC. The data showed that higher CYT was significantly associated with better clinical outcome, more antitumor infiltrating immune cells, fewer somatic copy number alterations, but a higher TMB (Tumor mutational burden) status. Furthermore, CYT-high EC was notably relevant to the high expression of various immune checkpoint molecules and showed more effective responses to ICB treatment. Taken together, this study provided new insights into the connection between diverse genetic events and the immune microenvironment in EC and indicated that the CYT status might be a promising biomarker to stratify patients with EC for ICB therapy.
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spelling pubmed-93139082022-07-26 Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma Chen, Qiang Wang, Chongyang Lei, Xinyi Huang, Ting Zhou, Renyu Lu, Yuanzhi J Oncol Research Article Immune checkpoint blockade (ICB) has been explored as a therapeutic strategy to recover the antitumor immune activities against endometrial cancer (EC) escaping from immune surveillance. Increasing evidence has indicated that microsatellite instability (MSI) is a promising biomarker to stratify patients for the ICB therapy. However, even in patients with MSI-High (MSI-H) endometrial cancers, PD-L1 inhibitors, avelumab, and durvalumab have shown only 27% of response rates. Therefore, there is an urgent need to discover new biomarkers for a predictive response to ICB therapy. In this study, we demonstrated that the immune cytolytic activity (CYT) index was significantly correlated with the development and response to immunotherapy in EC. The data showed that higher CYT was significantly associated with better clinical outcome, more antitumor infiltrating immune cells, fewer somatic copy number alterations, but a higher TMB (Tumor mutational burden) status. Furthermore, CYT-high EC was notably relevant to the high expression of various immune checkpoint molecules and showed more effective responses to ICB treatment. Taken together, this study provided new insights into the connection between diverse genetic events and the immune microenvironment in EC and indicated that the CYT status might be a promising biomarker to stratify patients with EC for ICB therapy. Hindawi 2022-07-18 /pmc/articles/PMC9313908/ /pubmed/35898926 http://dx.doi.org/10.1155/2022/9060243 Text en Copyright © 2022 Qiang Chen et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Qiang
Wang, Chongyang
Lei, Xinyi
Huang, Ting
Zhou, Renyu
Lu, Yuanzhi
Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma
title Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma
title_full Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma
title_fullStr Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma
title_full_unstemmed Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma
title_short Immune Cytolytic Activity for Comprehensive Insights of the Immune Landscape in Endometrial Carcinoma
title_sort immune cytolytic activity for comprehensive insights of the immune landscape in endometrial carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313908/
https://www.ncbi.nlm.nih.gov/pubmed/35898926
http://dx.doi.org/10.1155/2022/9060243
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