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

Pancreas. 2021 May-Jun;50(5):719-726. doi: 10.1097/MPA.0000000000001831.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B7-H1 Antigen / analysis
  • Biomarkers, Tumor / analysis
  • CD3 Complex / analysis
  • Female
  • Gastrointestinal Neoplasms / immunology*
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Neoplasms / surgery
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / immunology*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / surgery
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery
  • Programmed Cell Death 1 Receptor / analysis
  • Progression-Free Survival
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Time Factors
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD3 Complex
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor