Hepatocellular carcinoma (HCC) now ranks as the third most lethal tumor worldwide, which is also the highest incidence of primary liver cancer. HCC is often associated with risk factors including chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, fatty liver disease, alcohol, etc. Recently, immunotherapies with immune checkpoint inhibitors (ICIs) have shown strong anti-tumor activities in HCC, such as anti-cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and anti-programmed death 1 (PD-1). Given the high percentage of infiltrating lymphocytes and the high expression of programmed death 1 ligand 1 (PD-L1), immune checkpoint blockade therapies would be theoretically effective against HCC. The objective response rate (ORR) and disease control rate (DCR) of PD-1/PD-L1 inhibitors could achieve 16-36% and 54-74% respectively. However, in the context of nonalcoholic fatty liver disease (NAFLD), ICIs may not only deteriorate the prognosis but even aggravate liver damage by increasing the proportion of CD8+PD-1+ T cells and effector cytokines. Thus, addressing the resistance of ICIs will effectively improve the survival of HCC patients, which has become one of the urgent challenges in the application of immunotherapies.

This Research Topic aims to collect high-quality articles, including both original research and review articles on treatment effects or mechanisms of primary or acquired treatment resistance in liver cancer, especially in NASH-induced liver cancer. Contents may cover but are not limited to the following:

1) Novel discoveries on the mechanism of resistance to ICIs in liver cancer
2) Mechanisms of primary or acquired resistance to immunotherapies in liver cancer
3) Molecular and cellular characterizations of dynamic immune response in liver cancer
4) The tumor microenvironment and related response to immunotherapies in liver cancer
5) Novel effective combination therapy strategies for liver cancer

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

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Frontiers in Oncology

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