A pilot study of the immune microenvironment of GI neuroendocrine carcinoma.

Abstract

Gastroenteropancreatic high grade neuroendocrine carcinoma (GEP HG-NEC) is an aggressive malignancy with limited treatment options and increasing incidence in the United States. Due to the rarity of the cancer and heterogeneity of the primary tumor location, data on GEP HG-NEC oncogenesis and its interaction with the host immune system is limited. A greater understanding of GEP HG-NEC and its tumor microenvironment (TME) would benefit efforts to develop more effective targeted therapies and rationally adapt immunotherapy to this disease. In this study, we profiled the expression of 770 unique genes using 21 biopsy samples from patients with GEP HG-NEC using the NanoString nCounter PanCancer IO 360 platform. Our results show several trends evident within the GEP HG-NEC TME. Greater expression of genes indicative of immune cell infiltration was present within the TME of patients <60 years of age and in patients with greater overall survival (OS). Tumors from patients with non-pancreatic NEC had diminished MHCII expression compared to pancreatic NEC, suggesting more prominent adaptive immune responses in the pancreatic GEP HG-NEC subtype. Patients with a >6 month OS had tumors with elevated NK cell gene signatures compared to patients with poor survival. Further, the analysis revealed numerous differentially expressed genes based on patient age, tumor location, response to treatment, and OS which warrant future validation for assessing relationship with clinical outcomes in patients.