Immunotherapy of hepatocellular carcinoma: recent progress and new strategy

Abstract

Due to its widespread occurrence and high mortality rate, hepatocellular carcinoma (HCC) is an abhorrent kind of cancer. Immunotherapy is a hot spot in the field of cancer treatment, represented by immune checkpoint inhibitors (ICIs), which aim to improve the immune system’s ability to recognize, target and eliminate cancer cells. The composition of the HCC immune microenvironment is the result of the interaction of immunosuppressive cells, immune effector cells, cytokine environment, and tumor cell intrinsic signaling pathway, and immunotherapy with strong anti-tumor immunity has received more and more research attention due to the limited responsiveness of HCC to ICI monotherapy. There is evidence of an organic combination of radiotherapy, chemotherapy, anti-angiogenic agents and ICI catering to the unmet medical needs of HCC. Moreover, immunotherapies such as adoptive cellular therapy (ACT), cancer vaccines and cytokines also show encouraging efficacy. It can significantly improve the ability of the immune system to eradicate tumor cells. This article reviews the role of immunotherapy in HCC, hoping to improve the effect of immunotherapy and develop personalized treatment regimens.

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

“…Increased expression of MMP-9 was detected around the tumor capsule in HCC and was strongly correlated with tumor size, capsule status, tumor stage, and HCC recurrence risk ( Arii et al, 1996 ; Sun et al, 2005 ). An upregulated level of pro-inflammatory cytokine IL-6 was found in the serum of HCC patients ( Xu et al, 2021 ), and the IL-6/STAT3 signaling pathway has been frequently shown to be constitutively activated in HCC patients, which is associated with poor prognosis ( Li et al, 2023a ), affecting activities of anti-apoptosis, angiogenesis, proliferation, invasion, metastasis, and drug resistance of HCC cells ( Xu et al, 2021 ). IFN-γ produced by mucosa-associated invariant T (MAIT) cells was reduced in the peripheral blood and liver of HCC patients than in the controls ( Huang et al, 2021 ).…”

“…In recent years, immunotherapies in combination with conventional treatments such as anti-angiogenic drugs in HCC have achieved extraordinary success, although the effects of immunotherapy alone as treatment have been of relatively infrequent benefit. Here we only briefly introduce the most popular and well-accepted immunotherapies [reviewed elsewhere ( Oura et al, 2021 ; Li et al, 2023a )] in HCC.…”

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma –CLEAP 004 study

“…Significantly, the Chinese National Health Commission Guidelines for liver Cancer, along with esteemed institutes such as NCCN, CSCO, AASLD, and EASL, continuously prioritize immunotherapy-based combination regimens as the primary approaches for the initial treatment phase of advanced HCC ( 14 ). Despite the considerable long-term life advantages offered by immunotherapy in the treatment of hepatocellular carcinoma (HCC), tumors do exhibit progression ( 9 ), commonly referred to as primary or acquired drug resistance ( 4 , 7 , 8 , 15 ). The current diagnostic and risk stratification methods for predicting overall survival (OS) in the population following first immunotherapy are limited.…”

Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma

“…Cancer immunotherapy including immune checkpoint inhibitor and adoptive cell therapy has shown potential efficacy against cancers and also revolutionizing for HCC treatment. 5 Recently developed cell-based therapies have been applied to treat HCC, 6 and tumor-infiltrating T cell-based therapy has particularly received a lot of interest due to its attractive responses. 7 Natural killer (NK) cells exhibit potential tumor-killing efficacy against various tumor cells without cytokine syndrome through two major functions: (1) cell−cell interactiondependent cytotoxicity and (2) secretion of cytokines for immune modulation.…”

“…Cancer immunotherapy is effective and secure, leading to long-term survival for the treatment of solid tumors. Cancer immunotherapy including immune checkpoint inhibitor and adoptive cell therapy has shown potential efficacy against cancers and also revolutionizing for HCC treatment . Recently developed cell-based therapies have been applied to treat HCC, and tumor-infiltrating T cell-based therapy has particularly received a lot of interest due to its attractive responses …”