Immunotherapeutic strategies in gastroenteropancreatic neuroendocrine neoplasms: present condition and future...

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous malignancies frequently resistant to standard therapies. Immunotherapy represents a novel management frontier. This review synthesises clinical and translational evidence regarding immune checkpoint inhibitors (ICIs), bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cell therapies, and oncolytic virotherapy in GEP-NENs. We examine critical antigenic targets (somatostatin receptors, DLL3) and strategies to overcome the immunosuppressive tumour immune microenvironment (TIME). While single-agent ICIs show modest efficacy in well-differentiated NETs, dual checkpoint blockade exhibits durable disease control in poorly differentiated NECs. Targeted modalities like DLL3-directed bispecific antibodies demonstrate significant early efficacy. Furthermore, we summarise highly synergistic combinatorial approaches, specifically integrating immunotherapy with anti-angiogenic agents and peptide receptor radionuclide therapy (PRRT). Ongoing biomarker-driven trials and molecular profiling remain essential to optimise patient selection and treatment sequencing.