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Feng et al. Hepatoma Res 2021;7:3 Hepatoma Research
DOI: 10.20517/2394-5079.2020.107

Review Open Access

The immune microenvironment and progression
of immunotherapy and combination therapeutic

strategies for hepatocellular carcinoma

Zun-Yong Feng 1,2,# , Fang-Gui Xu , Yu Liu , Hao-Jun Xu , Fu-Bing Wu , Xiao-Bing Chen , Hong-Ping Xia 1,2,3
4
3
1
3,#
3
1 Department of Pathology, School of Basic Medical Sciences & State Key Laboratory of Reproductive Medicine & Key Laboratory
of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China.
2 Interdisciplinary Innovation Institute for Medicine and Engineering, Southeast University-Nanjing Medical University, Nanjing
211189, China.
3 Sir Run Run Hospital, Nanjing Medical University, Nanjing 21116, China.
4 Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.
# Contribute equally to this work.
Correspondence to: Dr. Hong-Ping Xia, Department of Pathology, School of Basic Medical Sciences & State Key Laboratory of
Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University,
Nanjing 211166, China. E-mail: xiahongping@njmu.edu.cn; Dr. Xiao-Bing Chen, Department of Medical Oncology, The Affiliated
Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China. E-mail: xiaobingchen01@163.com; Dr. Fu-Bing Wu, Sir
Run Run Hospital, Nanjing Medical University, Nanjing 21116, China. E-mail: wfbwkx@163.com

How to cite this article: Feng ZY, Xu FG, Liu Y, Xu HJ, Wu FB, Chen XB, Xia HP. The immune microenvironment and progression
Received: First Decision: Revised: Accepted: Published: of immunotherapy and combination therapeutic strategies for hepatocellular carcinoma. Hepatoma Res 2021;7:3.
http://dx.doi.org/10.20517/2394-5079.2020.107
Science Editor: Copy Editor: Production Editor: Jing Yu
Received: 14 Sep 2020 First Decision: 22 Sep 2020 Revised: 9 Oct 2020 Accepted: 20 Oct 2020 Published: 7 Jan 2021

Academic Editor: Sandi Alexander Kwee Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Hepatocellular carcinoma (HCC) accounts for 75%-85% of all primary liver cancers and is the leading cause
of cancer-related deaths. China accounts for almost half of the global incidence and deaths of HCC. The poor
response of chemotherapeutics and targeted drugs may be due to the drug resistance, heterogeneity of HCC,
severe chronic liver damage and cirrhosis. Restoration of the liver microenvironment changes caused by
chronic injury is crucial. Immunotherapy recently seems to show promise for the treatment of HCC induced by
inflammatory injury. However, the unique liver immune system and resident immune tolerance state also pose a
challenge for HCC immunotherapy. Different combinations of strategies have been developed for enhancement
of HCC treatment. Here, we will discuss the immune microenvironment and progression of immunotherapy and
combination therapeutic strategies for HCC.

Keywords: Immune microenvironment, immunotherapy, immune checkpoint inhibitors, Chimeric antigen receptor
T, hepatocellular carcinoma
© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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