Overcoming heterogeneity and immunosuppression: novel strategies in adoptive therapy for biliary tract cancer.

[BACKGROUND] Biliary tract cancer (BTC) is a highly heterogeneous malignancy originating from the biliary epithelium or gallbladder mucosa, characterized by strong invasiveness and poor prognosis. Although surgery remains the primary curative strategy, most patients are diagnosed at advanced stages, limiting surgical opportunities. The traditional gemcitabine plus cisplatin chemotherapy regimen, although a standard treatment, has limited efficacy and often leads to drug resistance. In recent years, adoptive cell immunotherapy has emerged as a promising new avenue for BTC treatment.

[MAIN BODY] This review systematically elaborates on the research progress of various ACT strategies in BTC, including chimeric antigen receptor T cells, tumor-infiltrating lymphocytes, natural killer cells, cytokine-induced killer cells, and T-cell receptor-engineered T cells. Furthermore, it comprehensively analyzes current key challenges and discusses future directions and optimization strategies regarding these therapies.

[CONCLUSION] This review summarizes recent progress in adoptive cell therapy for biliary tract cancer and discusses optimization strategies to facilitate clinical translation.