The Clinical Significance of PD-L1/PD-1 Expression in Gastroenteropancreatic Neuroendocrine Neoplasia.

Purpose: This study examined the tumor expression of programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) in patients with GEP-NEN. This study aims to reveal the relationship of their expression with clinicopathological characteristics and prognosis.

Methods: PD1 and PD-L1 expression in tumors from 120 GEP-MEN patients was evaluated using immunohistochemistry. The correlations of the expression of PDL1/PD1 and clinicopathological features were assessed.

Results: Immunohistochemical staining indicated that PD-L1 was expressed in the tumor cells of 52.5% patients with GEP-NENs, and PD-L1 expression was positively correlated with the World Health Organization (WHO) classification, American Joint Committee on Cancer (AJCC) stage, lymphatic metastasis and prognosis. Meanwhile, PD-1 was expressed in tumor infiltrating lymphocytes within 55.8% tumor samples, and PD-1 expression was positively correlated with AJCC stage and GEP-NENs prognosis. Moreover, survival analysis indicated that the overall median survival of patients with PD-L1/PD-1-positive tumors significantly differed from that of patients with PD-L1/PD-1-negative tumors. Multivariate analysis confirmed that AJCC stage and Chromogranin A expression in tumor tissues were independent prognostic factors for overall survival. In conclusion, PDL1 was an independent prognostic factor for patients with GEP-NENs. Our results suggested that patients with GEP-NENs might be appropriate for PD1/PDL1-targeted therapy.

Conclusions: Our findings show that the expression of PD-L1 and PD-1 correlates with patient prognosis, and may thus serve as potential pathological prognostic markers of GEP-NENs. Immunotherapy using PD-1/PD-L1 inhibitors may be a promising strategy for GEP-NENs patients with PD-L1/PD-1 positively expressed.