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

• Published in: Current opinion in oncology Vol. 27; no. 4; p. 338
• Main Authors: Tan, Yaohong, Garcia-Buitrago, Monica T, Trent, Jonathan C, Rosenberg, Andrew E
• Format: Journal Article
• Language: English
• Published: United States 01.07.2015
• Subjects: 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
• ISSN: 1531-703X
• DOI: 10.1097/CCO.0000000000000201

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. 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. 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.