T-Cell Subsets as Potential Biomarkers for Hepatobiliary Cancers and Selection of Immunotherapy Regimens as a Treatment Strategy

Patients with advanced hepatocellular or biliary cancers have a dismal prognosis with limited efficacy from standard systemic therapies. The benefit of precision medicine has so far been limited to a subset of biliary cancers, including FGFR rearrangements; hotspot mutations in IDH1/2, BRAF, and BRCA1/2; and other rare alterations. In contrast, hepatocellular carcinoma, an inflammation-driven cancer with an immune-infiltrated microenvironment, provides a promising opportunity for immunotherapy, compared with the highly desmoplastic immune desert or excluded stromal microenvironment in biliary cancers. The immune contexture in hepatobiliary cancers is mostly immunosuppressive, protumorigenic, and exhausted, which together with low tumor mutation burden and decreased neoantigens provides challenges for immunotherapy. A better understanding of the spatiotemporal profile of T cells within the tumor microenvironment and the dynamic interplay of immune modulators in the context of standard or experimental therapies is crucial to define additional markers of response and design evidence-based combinatorial regimens. This review considers recent literature in this area and highlights promising leads and emerging trends.

Automated summary

Patients with advanced hepatocellular or biliary cancers face a poor prognosis with limited efficacy from standard therapies. While precision medicine benefits a subset of biliary cancers, immunotherapy holds promise for hepatocellular carcinoma due to its immune-infiltrated microenvironment. The immunosuppressive and exhausted immune contexture in hepatobiliary cancers presents challenges for immunotherapy.