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Oncologic Trogocytosis Protects Tumour Stromal Cells from γδ Cell Cytotoxicity

Journal of Life Sciences 2011年第12期5卷 986-995页

作者： emilie decaup Pej man Mirshahi Arash Rafii Massoud Mirshahi Jean-Jacques Foumie Mary Poupot INSERM UMR1037-Cancer Research Center of Toulouse CNRS ERL CHU Purpan Toulouse 31024 France University of Toulouse 3 Toulouse 31000 France UMRS 872 INSERA/L University of Pierre et Marie Curie-Paris 6 and University of Paris Descartes Team 18 CRC 15 Rue del ＇Ecole de Mddecine Paris Cedex 06 75270 France Department of Genetic Medecine and Obstetrics and Gynecology WCMC-Qatar Doha Qatar

Tumours progressively develop chemoresistance and immunoescape abilities thanks to support from their stromal microenvironment. In ovarian carcinomas, for instance, tumour-associated mesenchymal stem cells (TAMC) can transfer multi-drug-resistant proteins to develop metastases. However, since the microenvironment of such carcinomas is frequently infiltrated by both TAMC and γδ T lymphocytes, the consequences of interactions between these cell types were unclear. Here, we report that whilst γδ T lymphocytes were not activated when co-incubated in vitro with TAMC, their cell membranes were trogocytosed by the TAMC. Since TAMC constitutively express a low level of HLA class I, which is increased by trogocytosis of γδ cell-derived HLA class I, the interaction increased the expression of HLA class-I molecules on TAMC. In addition, γδ T lymphocytes are HLA-unrestricted cytolytic cells and their activity is regulated by inhibitory receptors (KIR) for self-HLA class I. Hence, although the lytic activity of γδ T lymphocytes for unrelated target cells was unaffected by trogocytosis, it spared the TAMC. Therefore, interactions between TAMC and cytolytic γδ T cells avoided the killing of these stromal cells due to an active transfer of their protective HLA class-I molecules. These results suggest that trogocytosis contributes to the maintenance of cancer-associated stromal cells.

关键词：基质细胞肿瘤学细胞毒性保护 T淋巴细胞气象中心杀伤细胞相互作用

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