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Review
. 2022 Apr;24(4):451-461.
doi: 10.1007/s11912-022-01235-x. Epub 2022 Feb 16.

What Is the Status of Immunotherapy in Neuroendocrine Neoplasms?

Alejandro Garcia-Alvarez  1 , Jorge Hernando Cubero  2 , Jaume Capdevila  2
Affiliations
Review

What Is the Status of Immunotherapy in Neuroendocrine Neoplasms?

Alejandro Garcia-Alvarez et al. Curr Oncol Rep. 2022 Apr.

Abstract

Purpose of review: Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in neuroendocrine neoplasms (NENs) of gastro-entero-pancreatic origin.

Recent findings: PD-L1 staining by immunohistochemistry has shown heterogeneous results across different studies in both well-differentiated neuroendocrine tumors (NETs) and poorly-differentiated neuroendocrine carcinomas (NECs). Tumor mutational burden in NENs is low, but seems to be higher in NECs. Immune infiltrate (CD3+ lymphocytes) at the tumor microenvironment (TME) is present in NETs and NECs. However, results from clinical trials with immunotherapy as monotherapy o combinations have shown limited efficacy. Further investigation into new strategies aside from anti-CTLA-4/PD-1/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in NENs are more than needed in the near future.

Keywords: Immunotherapy; Neuroendocrine neoplasms; PD-L1; Tumor microenvironment; Tumor mutational burden.

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