Prognostic impact of PD-1 on tumor infiltrating lymphocytes in 433 resected esophageal cancers.

Abstract Background Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated antitumor effects in patients with various malignancies, including esophageal cancer. Thus, a better understanding of local immunity in esophageal cancer is crucial for improving treatment and clinical outcomes. Methods We evaluated PD-1 expression on TILs, as well as PD-L1 expression on cancer cells, by immunohistochemistry and immunofluorescence using a non-biased database of 433 curatively resected esophageal cancers. With the idea of application as liquid biopsy, PD-1 expression status on peripheral lymphocytes was evaluated by flow cytometry. Results The cutoff value of PD-1 expression was the median PD-1 count. Compared with cases of low PD-1 expression (n=219), cases with high levels of PD-1 expression (n=213) showed significantly worse overall survival (log rank P=0.0017). The prognostic effect of PD-1 differed according to the preoperative treatment status (P for interaction=0.040); PD-1 expression was associated with high overall mortality among patients without preoperative therapy, while no such association was present among those with preoperative treatment. A stratification based on PD-1 and PD-L1 status was also significantly associated with overall survival (log rank P=0.0005). PD-1 expression on TILs was significantly associated with that on peripheral lymphocytes (P Conclusions PD-1 expression on TILs was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. The combination of PD-1 and PD-L1 expression enabled further classification of patients according to clinical outcome.