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） ca...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.展开更多
文摘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.
