T-Cell Subsets as Potential Biomarkers for Hepatobiliary Cancers and Selection of Immunotherapy Regimens as a Treatment Strategy
Department of Pathology,
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Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.
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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.
Submitted February 15, 2021; final revision received July 28, 2021; accepted for publication September 22, 2021.
Disclosures: Dr. Kumar-Sinha has disclosed not receiving any financial consideration from any person or organization to support the preparation analysis, results, or discussion of this article. Dr. Sahai has disclosed serving as a Principal Investigator for Agios, Bristol-Myers Squibb, Celgene, Clovis, Exelixis, Fibrogen, Incyte, Ipsen, MedImmune, Merck, NCI, and Rafael; as a consultant and advisory board member for AstraZeneca, GlaxoSmithKline, Histosonics, Incyte, QED, and Rafael; and on the data safety monitoring board for Incyte.
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