Semin Liver Dis 2023; 43(04): 383-401
DOI: 10.1055/s-0043-1776127
Review Article

Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Xinpu Han*
1   Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China
Qianhui Sun*
1   Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China
Manman Xu*
1   Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China
Guanghui Zhu
1   Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China
Ruike Gao
1   Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China
Baoyi Ni
2   Department of Oncology, First Hospital of Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China
Jie Li
1   Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China
› Author Affiliations
Funding This research was supported by the National Natural Science Foundation of China (NSFC-81774289; NSFC-82074402; and NSFC-82204922).


Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively utilized, substantial hurdles have arisen for clinicians. These include countering ICIs resistance and ensuring precise efficacy assessments of these drugs, especially in the context of hepatocellular carcinoma (HCC). This review attempts to offer a holistic overview of the latest insights into the ICIs resistance mechanisms in HCC, the molecular underpinnings, and immune response. The intent is to inspire the development of efficacious combination strategies. This review also examines the unconventional response patterns, namely pseudoprogression (PsP) and hyperprogression (HPD). The prompt and rigorous evaluation of these treatment efficacies has emerged as a crucial imperative. Multiple clinical, radiological, and biomarker tests have been advanced to meticulously assess tumor response. Despite progress, precise mechanisms of action and predictive biomarkers remain elusive. This necessitates further investigation through prospective cohort studies in the impending future.

Author Contributions

Xinpu Han, Qianhui Sun, Manman Xu contributed to the investigation, methodology, data curation, and writing, review, and editing. Guanghui Zhu, Ruike Gao, and Baoyi Ni contributed to software, data curation. Jie Li contributed to methodology, supervision, and writing, review, and editing, resources, and funding acquisition.

* These authors contributed equally to this work and retain the first authorship.

Publication History

Article published online:
06 November 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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