title: The immune system and gastrointestinal stromal tumor: a wealth of opportunities.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDepartment of Pathology bDepartment of Medicine, University of Miami Miller School of Medicine, Jackson Memorial Hospital, and Sylvester Cancer Center, University of Miami Hospital, Miami, Florida, USA.
authors.forename: Yaohong
authors.initials: Y
authors.lastname: Tan
authors.forename: Monica T
authors.initials: MT
authors.lastname: Garcia-Buitrago
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trent
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Rosenberg
mesh_terms: D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D046152:Gastrointestinal Stromal Tumors / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007107:Immune System / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D060908:CTLA-4 Antigen