Increased infiltration of tissue-resident memory T cells predicts a good response to anti-PD-L1 immunotherapy in extrahepatic cholangiocarcinoma.

Background: Extrahepatic cholangiocarcinoma (eCCA) is an aggressive malignancy with a poor prognosis. Immune checkpoint inhibitors (ICIs) targeting PD-L1 enhance antitumor immunity, but reliable predictive biomarkers remain unclear. This study investigated tumor-infiltrating immune cells, including T cells and macrophages, as potential biomarkers for ICI efficacy in eCCA.

Methods: A retrospective analysis was conducted on 15 eCCA patients who received durvalumab for recurrent or unresectable disease after surgery. Immunohistochemical staining assessed PD-L1, HLA class I/II, CD8, and CD103 expression in resected tumor specimens. ICI response was evaluated using RECIST 1.1 criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Correlations between immune cell infiltration and clinical outcomes were analyzed.

Results: Five patients achieved PR, five SD, and five PD. CD8+ and CD103+ T cell infiltration within tumor nests was significantly higher in PR and SD groups than in PD (p=0.032, p=0.0147). High HLA class I expression correlated with response, while PD-L1 and HLA class II showed no significant association. Patients with increased CD8+CD103+ T cells demonstrated better disease control.

Conclusion: Intratumoral CD8+ and CD103+ T cells may serve as predictive biomarkers for ICI efficacy in eCCA, highlighting tissue-resident immune cells as therapeutic targets.