Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

Jian Chen; Julian A. Gingold; Xiaoping Su

doi:10.1016/j.molmed.2019.06.007

Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

Jian Chen, Julian A. Gingold, Xiaoping Su

Research output: Contribution to journal › Review article › peer-review

155 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant cancer. Dysregulated signaling in the transforming growth factor beta (TGF-β) pathway plays a central role in inflammation, fibrogenesis, and immunomodulation in the HCC microenvironment. This review dissects the genetic landscape of the TGF-β superfamily genes in HCC and discusses the essential effects of this pathway on the tumor immune microenvironment. We highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. An improved understanding of the detailed mechanisms of liver cancer immunogenicity and the specific role of TGF-β in mediating immunotherapy resistance in HCC will provide important insights into HCC immune escape and promote the development of biomarker-derived combination immunotherapies for HCC.

Original language	English (US)
Pages (from-to)	1010-1023
Number of pages	14
Journal	Trends in Molecular Medicine
Volume	25
Issue number	11
DOIs	https://doi.org/10.1016/j.molmed.2019.06.007
State	Published - Nov 2019

Keywords

TGF-β signaling
hepatocellular carcinoma
immune genomic profiling
immunotherapy
tumor microenvironment

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology

MD Anderson CCSG core facilities

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10.1016/j.molmed.2019.06.007

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title = "Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma",

abstract = "Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant cancer. Dysregulated signaling in the transforming growth factor beta (TGF-β) pathway plays a central role in inflammation, fibrogenesis, and immunomodulation in the HCC microenvironment. This review dissects the genetic landscape of the TGF-β superfamily genes in HCC and discusses the essential effects of this pathway on the tumor immune microenvironment. We highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. An improved understanding of the detailed mechanisms of liver cancer immunogenicity and the specific role of TGF-β in mediating immunotherapy resistance in HCC will provide important insights into HCC immune escape and promote the development of biomarker-derived combination immunotherapies for HCC.",

keywords = "TGF-β signaling, hepatocellular carcinoma, immune genomic profiling, immunotherapy, tumor microenvironment",

author = "Jian Chen and Gingold, {Julian A.} and Xiaoping Su",

note = "Funding Information: We thank Dr John R. Stroehlein for critical review and helpful suggestions on the manuscript. We thank Dr Xiaofan Lu for technical support. J.C. is an awardee supported by the AASLD Foundation Pinnacle Research Award in Liver Disease, the Texas Medical Center Digestive Diseases Center Pilot/Feasibility Project, and the Internal Research Grant (IRG) Program at The University of Texas MD Anderson Cancer Center . Publisher Copyright: {\textcopyright} 2019 The Author(s)",

year = "2019",

month = nov,

doi = "10.1016/j.molmed.2019.06.007",

language = "English (US)",

volume = "25",

pages = "1010--1023",

journal = "Trends in Molecular Medicine",

issn = "1471-4914",

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T1 - Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

AU - Chen, Jian

AU - Gingold, Julian A.

AU - Su, Xiaoping

N1 - Funding Information: We thank Dr John R. Stroehlein for critical review and helpful suggestions on the manuscript. We thank Dr Xiaofan Lu for technical support. J.C. is an awardee supported by the AASLD Foundation Pinnacle Research Award in Liver Disease, the Texas Medical Center Digestive Diseases Center Pilot/Feasibility Project, and the Internal Research Grant (IRG) Program at The University of Texas MD Anderson Cancer Center . Publisher Copyright: © 2019 The Author(s)

PY - 2019/11

Y1 - 2019/11

N2 - Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant cancer. Dysregulated signaling in the transforming growth factor beta (TGF-β) pathway plays a central role in inflammation, fibrogenesis, and immunomodulation in the HCC microenvironment. This review dissects the genetic landscape of the TGF-β superfamily genes in HCC and discusses the essential effects of this pathway on the tumor immune microenvironment. We highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. An improved understanding of the detailed mechanisms of liver cancer immunogenicity and the specific role of TGF-β in mediating immunotherapy resistance in HCC will provide important insights into HCC immune escape and promote the development of biomarker-derived combination immunotherapies for HCC.

AB - Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant cancer. Dysregulated signaling in the transforming growth factor beta (TGF-β) pathway plays a central role in inflammation, fibrogenesis, and immunomodulation in the HCC microenvironment. This review dissects the genetic landscape of the TGF-β superfamily genes in HCC and discusses the essential effects of this pathway on the tumor immune microenvironment. We highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. An improved understanding of the detailed mechanisms of liver cancer immunogenicity and the specific role of TGF-β in mediating immunotherapy resistance in HCC will provide important insights into HCC immune escape and promote the development of biomarker-derived combination immunotherapies for HCC.

KW - TGF-β signaling

KW - hepatocellular carcinoma

KW - immune genomic profiling

KW - immunotherapy

KW - tumor microenvironment

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DO - 10.1016/j.molmed.2019.06.007

M3 - Review article

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AN - SCOPUS:85071376967

SN - 1471-4914

VL - 25

SP - 1010

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JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

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ER -

Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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