Immunotherapy in Neuroendocrine Neoplasms: A Diamond to Cut

Simple Summary The development of new treatments for patients with neuroendocrine neoplasms (NENs) is imperative. Immunotherapy has shown efficacy in various neoplasms, such as small cell lung cancer and Merkel cell carcinoma. Although immunotherapy's effectiveness is more limited in NENs, combining immune checkpoint inhibitors with other therapeutic strategies like chemotherapy or targeted therapies could improve outcomes. Additionally, identifying predictive immune biomarkers could enhance patient selection. Our objective was to review the current evidence of immunotherapy in NENs, covering efficacy results and potential predictive biomarkers.Abstract A raise in the incidence of NENs is expected. Therefore, the identification of new therapeutic strategies, such as immunotherapy, remains crucial. To date, immune checkpoint inhibitors as monotherapy have shown modest activity in unselected NENs. Although immunotherapy combos (plus another immune agents or chemotherapy, among others) are potentially more active than single agents, this has not been uniformly confirmed, even in high-grade NENs. Other immunotherapeutic strategies under development include bispecific antibodies, targeting specific tumor antigens like DLL3, and cell therapy. Currently, no predictive immune biomarkers are available to guide clinical decisions. A comprehensive tumor molecular profiling approach needs to be developed for the selection of patients with NEN who could potentially benefit from immunotherapy. Ideally, clinical trials should incorporate this tumor molecular profiling to identify predictive biomarkers and improve efficacy. Achieving this goal requires an international collaborative effort.