Emerging biomarkers for immunotherapy response in biliary tract cancers: a comprehensive review of immune checkpoint inhibitor strategies

Abstract

Biliary tract cancers (BTCs) have rising incidence and mortality rates. Chemotherapy's limited efficacy has led to exploring new treatments like immunotherapy. which offers modest benefits. Moreover, the identification of reliable predictive biomarkers for immune checkpoint therapy in BTCs remains elusive, hindering personalized treatment strategies. This review provides an overview of the current landscape of emerging biomarkers for immunotherapy response in BTCs. We discuss the incremental benefits of combination therapy and the evolving role of immunotherapy in managing advanced BTC. Additionally, we highlight the need for robust predictive biomarkers to optimize treatment outcomes and foster a more individualized approach to patient care. We aim to identify promising research avenues and strategies to enhance therapeutic efficacy and patient survival in BTCs.

Keywords: PD-L1; biliary tract cancers; biomarkers; immune checkpoint inhibitor; microbiome; tumor microenvironment.

Graphical abstract

Figure 1.

Characterization and main immune components in the microenvironment of BTC. In the TME various cell types promote tumor progression and regulate immune activity, including infiltrating immune cells and cancer-associated fibroblasts, CAFs and extracellular components. TAM can attract immunosuppressive cells by secreting IL-4, IL-8, IL-10, CCL-2, CCL-22 and CCL-17. Th1 cells mediate antitumor immunity by producing IFN-γ and IL-2, which activate CD8⁺ T-cells and Th2 cells produce IL-4, IL-5 and IL-13. Endogenous CXCL9 regulates tumor-infiltrating NK cells to enhance antitumor immune surveillance. CAF: Cancer-associated fibroblast; CCL: Chemokine ligand: CXCL: Chemokine (C-X-C motif) ligand; IFN: Interferon; IL: Interleukin; NK: Natural killer; TAM: Tumor-associated macrophage; TME: Tumor microenvironment.