Immune cells in primary gastrointestinal stromal tumors

被引:29
作者
Cameron, Silke [1 ]
Haller, Florian [2 ]
Dudas, Joszef [1 ]
Moriconi, Federico [1 ]
Gunawan, Bastian [2 ]
Armbrust, Thomas [1 ]
Langer, Claus [3 ]
Fuezesi, Laszlo [2 ]
Ramadori, Giuliano [1 ]
机构
[1] Univ Gottingen, Univ Clin, Dept Gastroenterol & Endocrinol, D-37099 Gottingen, Germany
[2] Univ Gottingen, Univ Clin, Dept Gastroenteropathol, D-37099 Gottingen, Germany
[3] Univ Gottingen, Univ Clin, Dept Visceral & Transplant Surg, D-37099 Gottingen, Germany
关键词
dendritic cells; gastrointestinal stromal tumor; immune response;
D O I
10.1097/MEG.0b013e3282f3a403
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 proinflarnmatory 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/mm(2)) 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 (1196 217 cells/mm(2)). CD3 + T cells were the dominant lymphocytes (201 331 cells/mm(2)), whereas B cells (60 +/- 126cells/mm(2)) 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.
引用
收藏
页码:327 / 334
页数:8
相关论文
共 53 条
[1]   The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions [J].
Apte, Ron N. ;
Dotan, Shahar ;
Elkabets, Moshe ;
White, Malka R. ;
Reich, Eli ;
Carmi, Yaron ;
Song, Xiaping ;
Dvozkin, Tatyana ;
Krelin, Yakov ;
Voronov, Elena .
CANCER AND METASTASIS REVIEWS, 2006, 25 (03) :387-408
[2]   Inflammation and cancer: back to Virchow? [J].
Balkwill, F ;
Mantovani, A .
LANCET, 2001, 357 (9255) :539-545
[3]   In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas [J].
Bell, D ;
Chomarat, P ;
Broyles, D ;
Netto, G ;
Harb, GM ;
Lebecque, S ;
Valladeau, J ;
Davoust, J ;
Palucka, KA ;
Banchereau, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (10) :1417-1425
[4]   The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies [J].
Bingle, L ;
Brown, NJ ;
Lewis, CE .
JOURNAL OF PATHOLOGY, 2002, 196 (03) :254-265
[5]   Cellular responses to interferon-gamma [J].
Boehm, U ;
Klamp, T ;
Groot, M ;
Howard, JC .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :749-795
[6]   CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation [J].
Dalbeth, N ;
Gundle, R ;
Davies, RJO ;
Lee, YCG ;
McMichael, AJ ;
Callan, MFC .
JOURNAL OF IMMUNOLOGY, 2004, 173 (10) :6418-6426
[7]   The interplay between innate and adaptive immunity regulates cancer development [J].
de Visser, KE ;
Coussens, LM .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2005, 54 (11) :1143-1152
[8]   Monocyte/macrophage infiltration in tumors: modulators of angiogenesis [J].
Dirkx, Anita E. M. ;
Egbrink, Mirjam G. A. oude ;
Wagstaff, John ;
Griffioen, Arjan W. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (06) :1183-1196
[9]  
DONNELLY RP, 1993, J IMMUNOL, V151, P5603
[10]   IFN-γ-Inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking [J].
Dufour, JH ;
Dziejman, M ;
Liu, MT ;
Leung, JH ;
Lane, TE ;
Luster, AD .
JOURNAL OF IMMUNOLOGY, 2002, 168 (07) :3195-3204