Abstract
Neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are a heterogeneous family of neoplasms. Well-differentiated tumors are often slow growing and characterized by low tumor mutational burden. Poorly differentiated NECs are aggressive, with an increased mutational burden and higher propensity to express PD-L1. While the therapeutic landscape for neuroendocrine neoplasms (NENs) has evolved substantially over the past decade, immunotherapy has been unexplored in NENs until recently. Checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 agents, bi-specific tumor-targeting antibodies, and chimeric antigen receptor (CAR) T-cell therapy are examples of treatments that have demonstrated efficacy in other cancers and have recently been investigated in NENs. This review examines the immune landscape of NENs in detail, summarizes recent clinical study results, and discusses potential future directions for immunotherapy.