INTRODUCTION: 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. CONCLUSION: 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.
INTRODUCTION: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. CONCLUSION: 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.
Authors: Sylvie Rusakiewicz; Aurélie Perier; Michaela Semeraro; Jonathan M Pitt; Elke Pogge von Strandmann; Katrin S Reiners; Sandrine Aspeslagh; Christelle Pipéroglou; Frédéric Vély; Alexandre Ivagnes; Sarah Jegou; Niels Halama; Loic Chaigneau; Pierre Validire; Christos Christidis; Thierry Perniceni; Bruno Landi; Anne Berger; Nicolas Isambert; Julien Domont; Sylvie Bonvalot; Philippe Terrier; Julien Adam; Jean-Michel Coindre; Jean-François Emile; Vichnou Poirier-Colame; Kariman Chaba; Benedita Rocha; Anne Caignard; Antoine Toubert; David Enot; Joachim Koch; Aurélien Marabelle; Marion Lambert; Sophie Caillat-Zucman; Serge Leyvraz; Christian Auclair; Eric Vivier; Alexander Eggermont; Christophe Borg; Jean-Yves Blay; Axel Le Cesne; Olivier Mir; Laurence Zitvogel Journal: Oncoimmunology Date: 2016-04-25 Impact factor: 8.110
Authors: Vinod P Balachandran; Michael J Cavnar; Shan Zeng; Zubin M Bamboat; Lee M Ocuin; Hebroon Obaid; Eric C Sorenson; Rachel Popow; Charlotte Ariyan; Ferdinand Rossi; Peter Besmer; Tianhua Guo; Cristina R Antonescu; Takahiro Taguchi; Jianda Yuan; Jedd D Wolchok; James P Allison; Ronald P DeMatteo Journal: Nat Med Date: 2011-08-28 Impact factor: 53.440