Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion

Abstract The hepatocyte growth factor (HGF) along with its receptor (c-MET) are crucial in preserving standard cellular physiological activities, and imbalances in the c-MET signaling pathway can lead to the development and advancement of tumors. It has been extensively demonstrated that immune chec...

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Main Authors: Yang Xia, Chunye Huang, Min Zhong, Hongguang Zhong, Ruiwen Ruan, Jianping Xiong, Yangyang Yao, Jing Zhou, Jun Deng
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Cell Communication and Signaling
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Online Access:https://doi.org/10.1186/s12964-025-02033-1
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author Yang Xia
Chunye Huang
Min Zhong
Hongguang Zhong
Ruiwen Ruan
Jianping Xiong
Yangyang Yao
Jing Zhou
Jun Deng
author_facet Yang Xia
Chunye Huang
Min Zhong
Hongguang Zhong
Ruiwen Ruan
Jianping Xiong
Yangyang Yao
Jing Zhou
Jun Deng
author_sort Yang Xia
collection DOAJ
description Abstract The hepatocyte growth factor (HGF) along with its receptor (c-MET) are crucial in preserving standard cellular physiological activities, and imbalances in the c-MET signaling pathway can lead to the development and advancement of tumors. It has been extensively demonstrated that immune checkpoint inhibitors (ICIs) can result in prolonged remission in certain patients. Nevertheless, numerous preclinical studies have shown that MET imbalance hinders the effectiveness of anti-PD-1/PD-L1 treatments through various mechanisms. Consequently, clarifying the link between the c-MET signaling pathway and the tumor microenvironment (TME), as well as uncovering the effects of anti-MET treatment on ICI therapy, is crucial for enhancing the outlook for tumor patients. In this review, we examine the impact of abnormal activation of the HGF/c-MET signaling pathway on the control of the TME and the processes governing PD-L1 expression in cancer cells. The review thoroughly examines both clinical and practical evidence regarding the use of c-MET inhibitors alongside PD-1/PD-L1 inhibitors, emphasizing that focusing on c-MET with immunotherapy enhances the effectiveness of treating MET tumors exhibiting elevated PD-L1 expression.
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institution Kabale University
issn 1478-811X
language English
publishDate 2025-01-01
publisher BMC
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series Cell Communication and Signaling
spelling doaj-art-64fa5044d61a40c3a5a4858cf157d8072025-01-26T12:44:46ZengBMCCell Communication and Signaling1478-811X2025-01-0123111810.1186/s12964-025-02033-1Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasionYang Xia0Chunye Huang1Min Zhong2Hongguang Zhong3Ruiwen Ruan4Jianping Xiong5Yangyang Yao6Jing Zhou7Jun Deng8Department of Oncology, The First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The First Affiliated Hospital of Nanchang UniversityDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The First Affiliated Hospital of Nanchang UniversityDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The First Affiliated Hospital of Nanchang UniversityAbstract The hepatocyte growth factor (HGF) along with its receptor (c-MET) are crucial in preserving standard cellular physiological activities, and imbalances in the c-MET signaling pathway can lead to the development and advancement of tumors. It has been extensively demonstrated that immune checkpoint inhibitors (ICIs) can result in prolonged remission in certain patients. Nevertheless, numerous preclinical studies have shown that MET imbalance hinders the effectiveness of anti-PD-1/PD-L1 treatments through various mechanisms. Consequently, clarifying the link between the c-MET signaling pathway and the tumor microenvironment (TME), as well as uncovering the effects of anti-MET treatment on ICI therapy, is crucial for enhancing the outlook for tumor patients. In this review, we examine the impact of abnormal activation of the HGF/c-MET signaling pathway on the control of the TME and the processes governing PD-L1 expression in cancer cells. The review thoroughly examines both clinical and practical evidence regarding the use of c-MET inhibitors alongside PD-1/PD-L1 inhibitors, emphasizing that focusing on c-MET with immunotherapy enhances the effectiveness of treating MET tumors exhibiting elevated PD-L1 expression.https://doi.org/10.1186/s12964-025-02033-1CellularMesenchymal epithelial transition factor, Tumor microenvironment, PD1/PDL1 inhibitors, cMET inhibitors, HGF/cMET signaling pathway
spellingShingle Yang Xia
Chunye Huang
Min Zhong
Hongguang Zhong
Ruiwen Ruan
Jianping Xiong
Yangyang Yao
Jing Zhou
Jun Deng
Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion
Cell Communication and Signaling
Cellular
Mesenchymal epithelial transition factor, Tumor microenvironment, PD
1/PD
L1 inhibitors, c
MET inhibitors, HGF/c
MET signaling pathway
title Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion
title_full Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion
title_fullStr Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion
title_full_unstemmed Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion
title_short Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion
title_sort targeting hgf c met signaling to regulate the tumor microenvironment implications for counteracting tumor immune evasion
topic Cellular
Mesenchymal epithelial transition factor, Tumor microenvironment, PD
1/PD
L1 inhibitors, c
MET inhibitors, HGF/c
MET signaling pathway
url https://doi.org/10.1186/s12964-025-02033-1
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