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cancer cells. Flexibility of macrophages facilitates themselves to polarize according to different signals from
microenvironment. Macrophages mostly function as suppressive cells to inhibit proliferation and activation
of CTLs in HBV-related HCC, while promotes liver damage and fibrosis via releasing pro-inflammatory
cytokines.

Since there still remains lack of effective drug specifically targeting eradication of HBV or controlling
development of NAFLD, illustrating molecular mechanisms of immune cells and establishing novel
immunotherapies will provide promising options for treatment of HCC. Unbridling cytotoxic cells (ICI) and
stimulating the cells specifically engineered with tumor-associated antigens (CAR-T and CAR-NK) mutually
contribute to effectively restrain progression of HBV- and NAFLD-induced HCC. Taken together, the drug
resistance and adverse effect induced by immunotherapies should be further recorded and investigated in
future studies.

DECLARATIONS
Authors’ contributions
Conceived of the presented idea: Ma CH, Song XJ
Performed the basic writing: Song XJ
Developed the further revision: Ma CH

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by grants from the National Science Foundation of China (Key project 81830017
and 81902443), Taishan Scholarship (No.tspd20181201), National Key Research and Development Program
(2018YFE0126500), Shandong Provincial Key Innovation project (No.2018FYJH0503), Collaborative
Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of
Shandong.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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