Prognostic Implications of the Immune Tumor Microenvironment in Patients with Pancreatic and Gastrointestinal Neuroendocrine Tumors

Supplemental digital content is available in the text. Objectives The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS). Methods Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface. Results Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43–0.68; P < 0.0001), 0.45 (95% CI, 0.32–0.59; P = 0.0002), 0.50 (95% CI, 0.40–0.61; P < 0.0001), and 0.24 (95% CI, 0.03–0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19–0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68–5.91). Conclusions Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection.