Targets of immunotherapy for hepatocellular carcinoma: An update

Abstract

Hepatocellular carcinoma, the most common primary liver cancer, in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages. Although, surgical resection, ablation, liver transplant, and locoregional therapies are available for early stages; however, there are yet no effective treatment for advanced and recurrent tumors. Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression. However, still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment. At present, the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy, immune checkpoint therapy, adoptive cell transfer therapy, and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells. This review discusses the recent key development, the basis of drug resistance, immune evasion, immune tolerance, the available therapies based on stage of the tumor, and the ongoing clinical trials on immune checkpoint inhibitor therapy, adoptive cell transfer therapy, oncolytic viral vaccine therapy, and combination therapy.

Tumor-Infiltrating B Lymphocytes: Promising Immunotherapeutic Targets for Primary Liver Cancer Treatment

“…Further studies will help to establish whether ICB administration actively induces TLS formation, and if B lymphocytes and TLS creation have an active and beneficial role in immunotherapy response. In this way, clinical strategies based on drugs that modulate B lymphocytes or TLS formation have been studied extensively to fight solid tumors [ 102 , 106 , 107 ].…”

“…Current studies have demonstrated a marked heterogeneity in HCC tumors and highlighted that the crosstalk between cancer cells and the liver microenvironment promotes tumorigenesis and HCC pathogenesis, by pushing cell proliferation, survival, and the ability of migration and evasion [ 108 ]. In detail, the TME in HCC appears to be immunosuppressive, promoting the proliferation, invasion, and metastasis of tumors [ 106 , 107 ]. Thus, a better characterization of the immune landscape of HCC at high resolution would facilitate refining patient stratification and identify putative immune-therapeutic targets in order to develop novel therapies for HCC.…”

Hepatitis B virus pathogenesis relevant immunosignals uncovering amino acids utilization related risk factors guide artificial intelligence-based precision medicine

“…These findings suggest that the impact of PEG-IFN-α on improving liver function and inhibiting disease progression during HBV infection is closely related to the CLST-aCD4 axis, which requires further experimental verification. HCC is resistant to current therapies (Song et al, 2021;Rai and Mukherjee, 2022;Xia et al, 2022;Zhang et al, 2022), and a novel strategy that considers the immunology of the disease to improve treatment remains important (Donne and Lujambio, 2022;Rai and Mukherjee, 2022;Shen et al, 2022). Significant differences in sorafenib response between the CLST high aCD4 high and CLST low aCD4 low subgroups illustrated that CLST and aCD4 might be important biomarkers for optimizing the use of multi-kinase inhibitors for precision HCC treatment.…”

Clinical Analysis of Transcatheter Arterial Chemoembolization Sequential Microwave Ablation Combined with Targeted Therapy and Immunotherapy in the Treatment of Large Hepatocellular Carcinoma

“…Although TACE combined with MWA treatment can enhance the therapeutic effect of large hepatocellular carcinoma [3] [4], the synergistic action of anti-angiogenic targeted agents and immunotherapy drugs has significant advantages. By changing the Tumormicro-Environment (TME) [5], necrotic tumor cells after chemoembolization form new tumor-associated antigens to modulate the body's immune positivity. The anti-angiogenic targeted agents can prevent the reconstruction and regeneration of tumor vessels, and avoid the compensatory increase of Vascular Endothelial Growth Factor (VEGF) in a hypoxic environment after TACE [6].…”