Tumor Microenvironment Composition and Related Therapy in Hepatocellular Carcinoma

Zishuai Li; Zihan Zhang; Letian Fang; Jiayi Zhao; Zheyun Niu; Hongsen Chen; Guangwen Cao

doi:10.2147/JHC.S436962

Tumor Microenvironment Composition and Related Therapy in Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2023 Nov 21:10:2083-2099. doi: 10.2147/JHC.S436962. eCollection 2023.

Authors

Zishuai Li^#^{1

2

3}, Zihan Zhang^#⁴, Letian Fang^#^{1

2

3}, Jiayi Zhao^#^{1

2

3}, Zheyun Niu⁴, Hongsen Chen^{1

2

3}, Guangwen Cao^{1

2

3}

Affiliations

¹ Key Laboratory of Biological Defense, Ministry of Education, Second Military Medical University, Shanghai, 200433, People's Republic of China.
² Shanghai Key Laboratory of Medical Bioprotection, Second Military Medical University, Shanghai, 200433, People's Republic of China.
³ Department of Epidemiology, Second Military Medical University, Shanghai, 200433, People's Republic of China.
⁴ Department of Epidemiology, Tongji University School of Medicine Tongji University, Shanghai, 200120, People's Republic of China.

^# Contributed equally.

Abstract

Globally, primary liver cancer is the third leading cause of cancer death, and hepatocellular carcinoma (HCC) accounts for 75%-95%. The tumor microenvironment (TME), composed of the extracellular matrix, helper cells, immune cells, cytokines, chemokines, and growth factors, promotes the immune escape, invasion, and metastasis of HCC. Tumor metastasis and postoperative recurrence are the main threats to the long-term prognosis of HCC. TME-related therapies are increasingly recognized as effective treatments. Molecular-targeted therapy, immunotherapy, and their combined therapy are the main approaches. Immunotherapy, represented by immune checkpoint inhibitors (ICIs), and targeted therapy, highlighted by tyrosine kinase inhibitors (TKIs), have greatly improved the prognosis of HCC. This review focuses on the TME compositions and emerging therapeutic approaches to TME in HCC.

Keywords: hepatocellular carcinoma; immunotherapy; targeted therapy; tumor microenvironment.

Publication types

Review

Grants and funding

This work was supported by the GWV-10.1-XK17/3-year public health program of Shanghai Municipal Health Commission (GC), the National Key Basic Research Program of China [grant number 2015CB554006 (GC)], and the National Natural Science Foundation of China [grant numbers 91529305 (GC), 81520108021 (GC), 81673250 (GC)].