Immune cells in primary gastrointestinal stromal tumors.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Cameron
Silke
S
Department of Gastroenterology and Endocrinology, University Clinic of the Georg-August University, Göttingen, Germany.
Haller
Florian
F
Dudas
Joszef
J
Moriconi
Federico
F
Gunawan
Bastian
B
Armbrust
Thomas
T
Langer
Claus
C
Füzesi
Laszlo
L
Ramadori
Giuliano
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D016207:Cytokines; D019009:Proto-Oncogene Proteins c-kit; C067980:CD68 antigen, human; D000097382:CD68 Molecule