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Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response

A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment...

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Autores principales: Ling, Chen, Zhou, Xiuman, Gao, Yanfeng, Sui, Xinghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144862/
https://www.ncbi.nlm.nih.gov/pubmed/35631431
http://dx.doi.org/10.3390/ph15050605
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author Ling, Chen
Zhou, Xiuman
Gao, Yanfeng
Sui, Xinghua
author_facet Ling, Chen
Zhou, Xiuman
Gao, Yanfeng
Sui, Xinghua
author_sort Ling, Chen
collection PubMed
description A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment compositions of EAC to facilitate patient stratification and provide novel strategies to improve clinical outcomes. Here, we performed consensus molecular subtyping with nonnegative matrix factorization (NMF) using EAC data from the Cancer Genome Atlas (TCGA) and identified two distinct subtypes with significant prognostic differences and differences in tumor microenvironments. The findings were further validated in independent EAC cohorts and potential response to ICI therapy was estimated using Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap methods. Our findings suggest that EAC patients of subtype 2 with low levels of cancer-associated fibroblasts, tumor associated macrophages (TAMs), and MDSCs in the tumor microenvironment may benefit from PD-1 blockade therapy, while patients of subtype 1 are more responsive to chemotherapy or combination therapy. These findings might improve our understanding of immunotherapy efficacy and be useful in the development of new strategies to better guide immunotherapy and targeted therapy in the treatment of EAC.
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spelling pubmed-91448622022-05-29 Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response Ling, Chen Zhou, Xiuman Gao, Yanfeng Sui, Xinghua Pharmaceuticals (Basel) Article A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment compositions of EAC to facilitate patient stratification and provide novel strategies to improve clinical outcomes. Here, we performed consensus molecular subtyping with nonnegative matrix factorization (NMF) using EAC data from the Cancer Genome Atlas (TCGA) and identified two distinct subtypes with significant prognostic differences and differences in tumor microenvironments. The findings were further validated in independent EAC cohorts and potential response to ICI therapy was estimated using Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap methods. Our findings suggest that EAC patients of subtype 2 with low levels of cancer-associated fibroblasts, tumor associated macrophages (TAMs), and MDSCs in the tumor microenvironment may benefit from PD-1 blockade therapy, while patients of subtype 1 are more responsive to chemotherapy or combination therapy. These findings might improve our understanding of immunotherapy efficacy and be useful in the development of new strategies to better guide immunotherapy and targeted therapy in the treatment of EAC. MDPI 2022-05-14 /pmc/articles/PMC9144862/ /pubmed/35631431 http://dx.doi.org/10.3390/ph15050605 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 Article
Ling, Chen
Zhou, Xiuman
Gao, Yanfeng
Sui, Xinghua
Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
title Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
title_full Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
title_fullStr Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
title_full_unstemmed Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
title_short Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response
title_sort identification of immune subtypes of esophageal adenocarcinoma to predict prognosis and immunotherapy response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144862/
https://www.ncbi.nlm.nih.gov/pubmed/35631431
http://dx.doi.org/10.3390/ph15050605
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