Immunotherapy in Neuroendocrine Tumors: Challenges, Innovations, and Emerging Strategies

Neuroendocrine tumors (NETs) represent a diverse group of neoplasms arising from neuroendocrine cells, most commonly affecting the gastrointestinal tract, pancreas, and lungs. Despite advances in diagnostic tools and systemic therapies, including somatostatin analogs, targeted therapies, and peptide receptor radionuclide therapy (PRRT), treatment options for advanced or high-grade NETs remain limited, and durable responses are rare.Immunotherapy has revolutionized the treatment landscape of several solid tumors, yet its role in NETs remains under investigation. The immunologically “cold” tumor microenvironment of many NETs, coupled with their low mutational burden, has contributed to the modest activity of immune checkpoint inhibitors. Nonetheless, recent preclinical and early-phase clinical studies suggest that novel immunotherapeutic strategies, including adoptive cell therapy, bispecific T cell engagers, and immune modulation of the tumor microenvironment, hold promise in overcoming resistance and improving outcomes.In addition, this special issue will expand on one of the most clinically relevant and widely approved treatments for well differentiated NETs: PRRT. Beyond the established use of lutetium-177, we aim to explore emerging clinical trials investigating alpha-emitting isotopes, their potential benefits in higher-grade NETs, and the role of radiosensitizers in enhancing therapeutic efficacy. Furthermore, we encourage contributions on innovative combinations of PRRT with immunotherapeutic approaches, which may represent a future direction for improving patient outcomes.This special issue aims to provide a comprehensive overview of the current state and future directions of immunotherapy in neuroendocrine tumors. We welcome original research articles, reviews, and perspectives that explore immune checkpoint blockade, CAR-T cell therapy, bispecific antibodies, tumor microenvironment modulation, biomarkers of response, combination approaches, and translational models specific to NETs and NECs.Key topics may include:• Immune profiling of well-differentiated NETs and NECs• Mechanisms of immune evasion in NETs• Clinical trial updates and case series on checkpoint inhibitors in NETs• Novel immunotherapeutic agents in NETs, including bispecific T cell engagers, CAR-T therapies, and TILs• Predictive biomarkers and patient selection for immunotherapy• Combination strategies (e.g., immunotherapy with PRRT, antiangiogenics, chemotherapy, or radiosensitizers• Advances in PRRT, including lutetium-177, alpha-emitting isotopes, and application in high-grade NETsThrough this collection, we aim to highlight the current challenges and opportunities in applying PRRT and immunotherapy to this unique and complex class of tumors, and to stimulate collaborative efforts that can accelerate progress in the field. Topic editors: Eleonora Pelle, Menna Haider, MARINA TSOLI, Ana Valea Source: https://www.frontiersin.org/research-topics/76416/immunotherapy-in-neuroendocrine-tumors-challenges-innovations-and-emerging-strategies