Cargando…

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor functi...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yuanda, Li, Changfeng, Lu, Yaoping, Liu, Chang, Yang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630479/
https://www.ncbi.nlm.nih.gov/pubmed/36341377
http://dx.doi.org/10.3389/fimmu.2022.1016817
_version_ 1784823611733835776
author Liu, Yuanda
Li, Changfeng
Lu, Yaoping
Liu, Chang
Yang, Wei
author_facet Liu, Yuanda
Li, Changfeng
Lu, Yaoping
Liu, Chang
Yang, Wei
author_sort Liu, Yuanda
collection PubMed
description Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor function. As the tumor progresses, tumor immune tolerance is induced under the action of various factors, such that the tumor suppressor microenvironment is continuously transformed into a tumor-promoting microenvironment, which promotes tumor immune escape. Eventually, tumor cells manifest the characteristics of malignant proliferation, invasion, metastasis, and drug resistance. In recent years, stress effects of the extracellular matrix, metabolic and phenotypic changes of innate immune cells (such as neutrophils, mast cells), and adaptive immune cells in the tumor microenvironment have been revealed to mediate the emerging mechanisms of immune tolerance, providing us with a large number of emerging therapeutic targets to relieve tumor immune tolerance. Gastric cancer is one of the most common digestive tract malignancies worldwide, whose mortality rate remains high. According to latest guidelines, the first-line chemotherapy of advanced gastric cancer is the traditional platinum and fluorouracil therapy, while immunotherapy for gastric cancer is extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) and programmed death ligand 1 (PD-L1) targeted drugs, whose benefits are limited. Clinical experiments confirmed that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor receptor (VEGFR) and other targeted drugs alone or in combination with other drugs have limited efficacy in patients with advanced gastric cancer, far less than in lung cancer, colon cancer, and other tumors. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the immune tolerance of tumors is key to the success of gastric cancer immunotherapy. In this study, we summarize the latest mechanisms of various components of the tumor microenvironment in gastric cancer for inducing immune tolerance and promoting the formation of the malignant phenotype of gastric cancer, as well as the research progress of targeting the tumor microenvironment to overcome immune tolerance in the treatment of gastric cancer.
format Online
Article
Text
id pubmed-9630479
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96304792022-11-04 Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer Liu, Yuanda Li, Changfeng Lu, Yaoping Liu, Chang Yang, Wei Front Immunol Immunology Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor function. As the tumor progresses, tumor immune tolerance is induced under the action of various factors, such that the tumor suppressor microenvironment is continuously transformed into a tumor-promoting microenvironment, which promotes tumor immune escape. Eventually, tumor cells manifest the characteristics of malignant proliferation, invasion, metastasis, and drug resistance. In recent years, stress effects of the extracellular matrix, metabolic and phenotypic changes of innate immune cells (such as neutrophils, mast cells), and adaptive immune cells in the tumor microenvironment have been revealed to mediate the emerging mechanisms of immune tolerance, providing us with a large number of emerging therapeutic targets to relieve tumor immune tolerance. Gastric cancer is one of the most common digestive tract malignancies worldwide, whose mortality rate remains high. According to latest guidelines, the first-line chemotherapy of advanced gastric cancer is the traditional platinum and fluorouracil therapy, while immunotherapy for gastric cancer is extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) and programmed death ligand 1 (PD-L1) targeted drugs, whose benefits are limited. Clinical experiments confirmed that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor receptor (VEGFR) and other targeted drugs alone or in combination with other drugs have limited efficacy in patients with advanced gastric cancer, far less than in lung cancer, colon cancer, and other tumors. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the immune tolerance of tumors is key to the success of gastric cancer immunotherapy. In this study, we summarize the latest mechanisms of various components of the tumor microenvironment in gastric cancer for inducing immune tolerance and promoting the formation of the malignant phenotype of gastric cancer, as well as the research progress of targeting the tumor microenvironment to overcome immune tolerance in the treatment of gastric cancer. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9630479/ /pubmed/36341377 http://dx.doi.org/10.3389/fimmu.2022.1016817 Text en Copyright © 2022 Liu, Li, Lu, Liu and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Liu, Yuanda
Li, Changfeng
Lu, Yaoping
Liu, Chang
Yang, Wei
Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
title Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
title_full Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
title_fullStr Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
title_full_unstemmed Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
title_short Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
title_sort tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630479/
https://www.ncbi.nlm.nih.gov/pubmed/36341377
http://dx.doi.org/10.3389/fimmu.2022.1016817
work_keys_str_mv AT liuyuanda tumormicroenvironmentmediatedimmunetoleranceindevelopmentandtreatmentofgastriccancer
AT lichangfeng tumormicroenvironmentmediatedimmunetoleranceindevelopmentandtreatmentofgastriccancer
AT luyaoping tumormicroenvironmentmediatedimmunetoleranceindevelopmentandtreatmentofgastriccancer
AT liuchang tumormicroenvironmentmediatedimmunetoleranceindevelopmentandtreatmentofgastriccancer
AT yangwei tumormicroenvironmentmediatedimmunetoleranceindevelopmentandtreatmentofgastriccancer