Dr. Pinato on Molecular Characterization of Tumor Microenvironment in NETs

David J. Pinato, MD, PhD, clinical senior lecturer in medical oncology, clinician scientist, consultant medical oncologist, Department of Surgery and Cancer, Imperial College London, discusses the molecular makeup of the tumor microenvironment in neuroendocrine malignancies.

Although neuroendocrine tumors (NETs) are a rare subtype of solid malignancies, increased awareness is leading to increased prevalence of this tumor subtype, says Pinato. For patients with slow-growing, low-grade NETs, treatment with somatostatin analogs is possible but patients will eventually progress, he adds. There is a delicate balance that must be found in the management of long-term survivors.

Using a retrospective approach, Pinato and colleagues looked at over 100 patients with neuroendocrine tumors of various sites and grades and examined the interaction between the activation of hypoxia and the expression of antitumor immunity markers, such as PD-L1 and Indoleamine-deoxygenase-1 (IDO-1), as they represent an immunosuppressive microenvironment.

Results showed independence between the two domains; expression of VEGF-A, Hif-1α, and Carbonic Anhydrase-IX—biomarkers of hypoxia—are independent from PD-L1 expression and other actionable drivers of anticancer immunity, says Pinato.

Pinato and his team also examined the expression of circulating tumor cells and found that 75% of patients had overexpression of PD-L1. Those patients who tested positively also had further disease advancement with a higher tumor burden. These findings support a potential therapeutic role for PD-L1/IDO-1 inhibitors in a subset of NETS, but further exploration is needed, Pinato concludes.