Defining Tumor Microenvironment as a Possible Target for Effective GEP-NENs Immunotherapy-A Systematic Review

Area of Science:

• Oncology
• Immunology
• Gastroenterology

Background:

• Neuroendocrine neoplasms (NENs) are diverse malignancies, with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) being the most common type.
• Optimal treatment strategies for GEP-NETs remain challenging due to their varied origins and characteristics.
• The tumor microenvironment (TME) significantly influences cancer development and response to therapy, necessitating a deeper understanding in GEP-NETs.

Purpose of the Study:

• To characterize the tumor immune microenvironment (TME) in GEP-NETs.
• To explore potential immunotherapeutic strategies for GEP-NETs based on TME composition.
• To synthesize current research on immune cell infiltrates, immune checkpoints, cytokines, neoangiogenesis, and the microbiome within the GEP-NET TME.

Main Methods:

• Systematic review of scientific literature.
• Searches conducted in PubMed, Web of Science, and Scopus databases.
• Adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Main Results:

• 28 relevant articles were included from an initial search of 3800 publications.
• The review synthesizes data on immune cell populations, immune checkpoint expression, cytokine profiles, neoangiogenesis, and microbiome composition in GEP-NET TME.
• Key factors influencing the GEP-NET TME and their correlation with the immune system were identified.

Conclusions:

• Characterizing the GEP-NET TME is crucial for advancing targeted immunotherapies.
• Further research into the immune landscape of GEP-NETs can guide the development of more effective treatment options.
• Understanding the interplay between tumor cells and the immune system within the TME is essential for improving patient outcomes.