Circulating PD-L1 is associated with T cell infiltration and predicts prognosis in patients with CRLM following hepatic resection.

Abstract

Exosomal PD-L1 (exoPD-L1) could induce immunosuppression functionally, thus impairing patients' survival in melanoma, NSCLC, and gastric cancer. However, no evidence demonstrates the feasibility of circulating exoPD-L1 and soluble PD-L1 (sPD-L1) as biomarkers for prognosis and early recurrence in colorectal liver metastasis (CRLM) patients following hepatectomy or their association with T cell infiltration at liver metastases. In cohort 1, exoPD-L1 and sPD-L1 were preoperatively tested using ELISA. CD3, CD8, granzyme B (GB) and PD1 expressed at liver metastases were evaluated using immunohistochemistry. In cohort 2, exoPD-L1 and sPD-L1 were detected at baseline, before hepatectomy, after hepatectomy, and after disease progression. In cohort 1, higher preoperative exoPD-L1 or sPD-L1 significantly impaired RFS (exoPD-L1, P=0.0043; sPD-L1, P=0.0041) and OS (exoPD-L1, P=0.0034; sPD-L1, P=0.0061). Furthermore, preoperative exoPD-L1 was negatively correlated with CD3+T-lymphocytes infiltrated at tumor center (CT), and GB and PD1 were expressed at tumor invasive margin (IM). Preoperative sPD-L1 was negatively correlated with CD3+and CD8+T-lymphocytes' infiltration at IM and CT, GB and PD1 expression at IM. In cohort 2, exoPD-L1 and sPD-L1 levels decreased following hepatectomy but increased when tumor progressed. Moreover, higher postoperative exoPD-L1 and sPD-L1 or a small reduction in exoPD-L1 and sPD-L1 levels after hepatectomy suggested higher early recurrence rate. Both preoperative exoPD-L1 and sPD-L1 had promising prognostic values and were associated with T cell infiltration at liver metastases in CRLM patients following hepatectomy. Dynamically tracking exoPD-L1 and sPD-L1 levels could monitor disease status and detect early recurrence.