The immune system and gastrointestinal stromal tumor: a wealth of opportunities

Curr Opin Oncol. 2015 Jul;27(4):338-42. doi: 10.1097/CCO.0000000000000201.

Abstract

Purpose of review: This article reviews the current literature on tumor-infiltrating immune cells in gastrointestinal stromal tumor (GIST), and the current status and prospects of effective immunotherapeutic strategies.

Recent findings: Tumor-infiltrating immune cells populate the microenvironment of GISTs; the most numerous are tumor-associated macrophages (TAMs) and CD3 T cells. TAMs have not been shown to have a relationship with the biological behavior of GISTs; however, the number of CD3 T cells correlates with better outcomes. The prognostic significance of tumor-infiltrating neutrophils, natural killer cells, CD4 T cells, CD8 T cells, and Treg cells remains unknown.Imatinib mesylate achieves a clinical response in 80% of patients with GIST. Its antitumor mechanism is partially immune mediated. The combination of imatinib and interferon-α has been shown to be effective against GIST - it eradicates tumor cells including those that are drug resistant. Preclinical trials including cytotoxic T lymphocyte-associated antigen 4 blockade, anti-KIT antibody, and the generation of designer T cells have shown promising therapeutic effect in animal models of GIST.

Summary: GIST contains many tumor-infiltrating immune cells and should be susceptible to immunotherapy; early clinical and preclinical trials have shown promising results that should lead to new investigations and effective forms of direct and synergistic therapies.

Publication types

  • Review

MeSH terms

  • CD3 Complex / immunology
  • CTLA-4 Antigen / immunology
  • Gastrointestinal Stromal Tumors / immunology*
  • Gastrointestinal Stromal Tumors / pathology
  • Gastrointestinal Stromal Tumors / therapy
  • Humans
  • Immune System / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Macrophages / immunology
  • Macrophages / pathology
  • Models, Animal
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Tumor Microenvironment / immunology*

Substances

  • CD3 Complex
  • CTLA-4 Antigen