The Immune Response in Gastrointestinal Stromal Tumors

Background: Gastrointestinal stromal tumors (GISTs) are the most frequent tumors with mesenchymal origin at the level of the digestive tract. Assessment of intratumoral immune cells can provide valuable prognostic information and may contribute to the development of targeted immune therapies for selected cases. Here in we evaluated the inflammatory infiltrate in gastrointestinal stromal tumors, the ratios between cytotoxic and helper T cells and their prognostic significance. Methods: We retrospectively analysed 25 cases of GISTs and extragastrointestinal stromal tumors (EGISTs). Immunohistochemical testing for CD3, CD4, CD8, CD20 and CD68 was performed to emphasize the immune cells. Inflammatory cells were quantified with the help of ImageJ software. Statistical analysis was performed to search for correlation between the immune response and clinical-pathological and prognostic variables. Results: GISTs were in all cases infiltrated with immune cells in variable amount. The pattern of distribution was diffuse or in aggregates, most frequent around blood vessels. Gastric tumors had the largest amount of inflammatory infiltrate and EGISTs the lowest. The dominant intratumoral immune cells were represented by lymphocytes, with fewer plasma cells, histiocytes, eosinophils, neutrophils and mast cells. CD3+ lymphocytes were the most common subtype. In 9 cases the CD8+/CD4+ ratio was subunitary. An increased number of histiocytes were associated with a high risk of disease progression. No other correlation between immune cells and other prognostic factors were established. Conclusion: Gastrointestinal stromal tumors represent the site of complex interactions between various types of immune cells and neoplastic cells. Accumulation of CD68+ cells correlates with high risk GISTs. Our paper provides an overview on the inflammation in this tumor type and further studies are necessary for more comprehensive results.