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 within CD8 PD-1 T cells significantly correlated with advanced TNM stage (P = 0.035). ICC patients with high proportion of CD8 PD-1 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 (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 T cells may cooperatively play a role in inhibiting anti-tumor immunity.

CONCLUSION

CD68 PD-L1 macrophages and CD8 PD-1 T cells predict unfavorable prognosis, which could also bring new progress about immune target therapy in ICC research.