Abstract
OBJECTIVE: Immunotherapy targeting the programmed cell death protein-1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) pathway has been observed to be efficient in several solid tumors. We aim to investigate the prognostic significance of PD-1/PD-L1 expression profile in intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: We investigated the expression of PD-1, PD-L1, CD8(+) T cells, and CD68(+) macrophages in paired tumor and adjacent normal tissues from 322 ICC patients using tyramide signal amplification (TSA)-based multiplexed immunohistochemistry. RESULTS: We found that high proportion of tumor-infiltrating CD8(+) PD-1(High) within CD8(+) PD-1(+) T cells significantly correlated with advanced TNM stage (P = 0.035). ICC patients with high proportion of CD8(+) PD-1(High) in CD8(+) PD-1(+) had worse postoperative survival than low proportion patients (P = 0.0037), which was an independently prognostic factor for OS (P = 0.025,). The density of CD68(+) PD-L1(+) significantly and positively correlated with the density of CD8(+) PD-1(High) (P < 0.0001, r = 0.5927). The proportion of CD68(+) PD-L1(+) within CD68(+) ICC was the risk factor for OS and TTR but not an independently factor for prognosis. The CD68(+) PD-L1(+) macrophages and CD8(+) PD-1(High) T cells may cooperatively play a role in inhibiting anti-tumor immunity. CONCLUSION: CD68(+) PD-L1(+) macrophages and CD8(+) PD-1(High) T cells predict unfavorable prognosis, which could also bring new progress about immune target therapy in ICC research.