Corvaisier Murielle, Moreau-Aubry Agnès, Diez Elisabeth, Bennouna Jaafar, Mosnier Jean-Francois, Scotet Emmanuel, Bonneville Marc, Jotereau Francine
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 601, Nantes, France.
J Immunol. 2005 Oct 15;175(8):5481-8. doi: 10.4049/jimmunol.175.8.5481.
During analysis of CD8 T cells derived from ascites of a colon cancer patient, we isolated a Vgamma9Vdelta2 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 Vgamma9Vdelta2 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 Vgamma9Vdelta2 T cells of various origins, and Vgamma9Vdelta2 lymphocytes were present in the majority of colon tumor samples studied. Together, these results suggest that Vgamma9Vdelta2 T cells contribute to the natural immune surveillance against colon cancers. Therefore, this study provides a strong rationale for the use of Vgamma9Vdelta2 T cell agonists in immunotherapies targeting colon tumors.
在对一名结肠癌患者腹水中的CD8 T细胞进行分析时，我们分离出了一个Vγ9Vδ2 T细胞克隆，该克隆对自体肿瘤细胞系表现出强烈反应性。该克隆杀死了大部分同种异体结肠癌和黑色素瘤细胞系，但不影响正常结肠细胞系、结肠成纤维细胞或黑色素细胞。肿瘤细胞识别依赖于TCR和NKG2D，并诱导该克隆分泌TNF-α和IFN-γ；相应地，肿瘤靶标表达了几种NKG2D配体，如MHC I类链相关基因A和UL16结合蛋白分子。Vγ9Vδ2 T细胞对结肠肿瘤的识别高度依赖于靶细胞的异戊烯基焦磷酸产生和ICAM-1表达。最后，使用各种来源的多克隆Vγ9Vδ2 T细胞观察到了针对结肠癌细胞系的类似反应模式，并且在所研究的大多数结肠肿瘤样本中都存在Vγ9Vδ2淋巴细胞。总之，这些结果表明Vγ9Vδ2 T细胞有助于对结肠癌的天然免疫监视。因此，本研究为在针对结肠肿瘤的免疫治疗中使用Vγ9Vδ2 T细胞激动剂提供了有力的理论依据。
