Vγ9Vδ2 T cell response to colon carcinoma cells
Vγ9Vδ2 T cell response to colon carcinoma cells
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DOI：
10.4049/jimmunol.175.8.5481
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发表时间：
2005-10-15
影响因子：
4.4
通讯作者：
Jotereau, F
中科院分区：
文献类型：
--
作者：
Corvaisier, M;Moreau-Aubry, A;Jotereau, F
在对一例结肠癌患者腹水中CD8T细胞的分析中，我们分离到一个V-Gamma 9V-Delta-2T细胞克隆，该克隆对自体肿瘤细胞具有很强的反应性。这种克隆杀死了很大一部分同种异体结肠癌和黑色素瘤细胞系，但不影响正常的结肠癌细胞系、结肠成纤维细胞或黑素细胞。肿瘤细胞的识别依赖于TCR和NKG2D，并通过克隆诱导肿瘤细胞分泌肿瘤坏死因子-α和干扰素-γ；相应地，肿瘤靶点表达多个NKG2D配体，如MHC-I类链相关基因A和UL16结合蛋白分子。V-Gamma 9V Delta 2T细胞对结肠癌的识别高度依赖于靶细胞产生的异戊烯焦磷酸和ICAM-1的表达。最后，用不同来源的多克隆V-Gamma 9V Delta-2 T细胞对结肠癌细胞株也观察到了类似的反应模式，并且大多数结肠癌样本中都存在V-Gamma 9V-Delta 2淋巴细胞。综上所述，这些结果表明，V-Gamma 9V-Delta2T细胞有助于对结肠癌的自然免疫监视。因此，这项研究为在针对结肠肿瘤的免疫治疗中使用V-Gamma 9V Delta 2 T细胞激动剂提供了强有力的理论依据。
During analysis of CD8 T cells derived from ascites of a colon cancer patient, we isolated a V gamma 9V delta 2 T cell clone showing strong reactivity against autologous tumor cell lines. This clone killed a large fraction of allogeneic colon carcinoma and melanoma cell lines, but did not affect a normal colon cell line, colon fibroblasts, or melanocytes. Tumor cell recognition was TCR and NKG2D dependent and induced TNF-alpha and IFN-gamma secretion by the clone; accordingly, tumor targets expressed several NKG2D ligands, such as MHC class I chain-related gene A and UL16-binding protein molecules. Colon tumor recognition by V gamma 9V delta 2 T cells was highly dependent on isopentenyl pyrophosphate production and ICAM-1 expression by target cells. Finally, similar reactivity patterns against colon carcinoma cell lines were observed using polyclonal V gamma 9V delta 2 T cells of various origins, and V gamma 9V delta 2 lymphocytes were present in the majority of colon tumor samples studied. Together, these results suggest that V gamma 9V delta 2 T cells contribute to the natural immune surveillance against colon cancers. Therefore, this study provides a strong rationale for the use of V gamma 9V delta 2 T cell agonists in immunotherapies targeting colon tumors.