The tumor microenvironment of hepatocellular carcinoma and its targeting strategy by CAR-T cell immunotherapy

Abstract

Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, which ranks sixth in cancer incidence and third in mortality. Although great strides have been made in novel therapy for HCC, such as immunotherapy, the prognosis remains less than satisfactory. Increasing evidence demonstrates that the tumor immune microenvironment (TME) exerts a significant role in the evolution of HCC and has a non-negligible impact on the efficacy of HCC treatment. In the past two decades, the success in hematological malignancies made by chimeric antigen receptor-modified T (CAR-T) cell therapy leveraging it holds great promise for cancer treatment. However, in the face of a hostile TME in solid tumors like HCC, the efficacy of CAR-T cells will be greatly compromised. Here, we provide an overview of TME features in HCC, discuss recent advances and challenges of CAR-T immunotherapy in HCC.

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.…”

“…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. For this reason, targeting the TME with new immunotherapy strategies (including vaccines, antibodies, immune checkpoint inhibitors, and adoptive cell therapy (ACT)) is the pivotal goal for HCC treatment [ 107 ]. Furthermore, the immunological classification could guide immunotherapy for HCC, thus deciding to administer an agonist antibody for the immunosuppressive subtype or immune checkpoint inhibitors (as PD-1 blocking antibody) for the immunoreactive subtype [ 113 ].…”

Investigating the hepatoprotective potentiality of marine-derived steroids as promising inhibitors of liver fibrosis

“…Similarly, while CEA levels may be increased in some cases of liver brosis in rats, it is not a reliable marker for the disease and cannot be used as a diagnostic tool. 12 Several prior research have reported the anti-cancer activity of so corals against several forms of cancer, including breast, lung, colon, and liver cancer. 20 Because of its different modes of action in liver cancer, the group treated with silymarin following development of liver brosis demonstrated improvement in AFP and CEA when compared to the acetaminophen group.…”

Editorial: Complexity of tumor microenvironment: A major culprit in cancer development

“…The latter involves manipulating T cells in the laboratory to add artificial receptors that can invoke attacks against cancer cells ( 32 – 34 ). However, CAR-T therapy remains limited by the lack of appropriate targets in solid tumors ( 33 , 35 – 37 ). However, advanced-stage patients or those presenting with unfavorable tumors inevitably face disease progression with dire outcomes ( 38 – 40 ).…”