Immune cells in primary gastrointestinal stromal tumors

• DOI: 10.1097/meg.0b013e3282f3a403
• Publication Date: 2009-03-05T15:46:30Z
• Authors: Silke Cameron; Florian Haller; Joszef Dudas; Federico Moriconi; Bastian Gunawan; Thomas Armbrust; Claus Langer; Laszlo Füzesi; Giuliano Ramadori
• Keywords: Adult; Aged, 80 and over; Male; CD3 Complex; Gastrointestinal Stromal Tumors; 610; Antigens, Differentiation, Myelomonocytic; Cell Communication; Dendritic Cells; Middle Aged; Antigens, CD3; 3. Good health; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Cell Transformation, Neoplastic; Phenotype; 0302 clinical medicine; Antigens, CD; Cytokines; Humans; Female; Stromal Cells; Aged

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are regarded as having relatively uniform histology, although their potential for malignant behavior varies. Despite a strong promoting role of tumor-infiltrating innate immune cells in neoplastic progression, the presence of immune cells in GISTs has not yet been studied.A total of 47 untreated, c-kit-positive primary GISTs were immunohistochemically analyzed to distinguish histiocytic and dendritic cells (DCs) (KIM-1P, fascin, and CD68) from cells of lymphoplasmacellular origin (CD3, CD20, and CD56). Furthermore, the gene expression of proinflammatory cytokines was characterized by real-time, reverse transcription-PCR analysis of total RNA extracted from frozen tissue samples.KIM-1P+ cells were the dominant immune cells (851+/-295 cells/mm2) and were scattered among the tumor cells. Most of the KIM-1P+ cells showed cellular projections characteristic of DCs. Fascin positivity identified a subgroup of DCs. In comparison to KIM-1P+ cells, there were significantly fewer CD68+ macrophages (196+/-217 cells/mm2). CD3+ T cells were the dominant lymphocytes (201+/-331 cells/mm2), whereas B cells (60+/-126 cells/mm2) were few. On transcriptional level, a concomitant gene expression of cytokines for the classical acute phase cytokines TNF-alpha and IL-6 was missing, thus supporting the rather innate status of immune cells.GISTs contain, beside T lymphocytes, a high number of monocyte-derived cells, which we suggest are, at least in part, immature DCs. Together with the lack of gene expression of inflammatory cytokines in tumor tissue our results point to a possible 'symbiotic relationship' between the tumor and the local immune cells.