Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB.
Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB.
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DOI：
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发表时间：
1999
影响因子：
11.1
通讯作者：
V. Groh;R. Rhinehart;H. Secrist;S. Bauer;K. Grabstein;T. Spies
中科院分区：
文献类型：
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作者：
V. Groh;R. Rhinehart;H. Secrist;S. Bauer;K. Grabstein;T. Spies
人MHC I类相关分子云母和MICB是应激诱导的抗原，其被表达可变区Vdelta 1的γ δ T细胞亚群识别。已经发现这种功能关联仅限于肠上皮，其中这些T细胞是普遍存在的，并且其中云母和推测的MICB主要表达。然而，已在各种上皮肿瘤中观察到V δ 1 γ δ T细胞的频率增加;此外，云母/B在各种培养的上皮肿瘤细胞上表达。用新鲜分离的肿瘤标本，云母/B的表达在许多但不是全部的肺癌、乳腺癌、肾癌、卵巢癌、前列腺癌和结肠癌中被记录。在云母/B阳性的肿瘤中，V δ 1 γ δ T细胞的频率显著高于阴性的肿瘤。来源于不同肿瘤的V δ 1 γ δ T细胞系和克隆识别自体和异源肿瘤细胞上的云母/B。在与以前的证据雅阁，没有观察到这些相互作用的限制，如由特定的肽配体施加的那些。因此，云母/B是肿瘤相关抗原，其可以以明显无条件的方式被肿瘤浸润性γ δ T细胞亚群识别。这些结果提高了可能性，即通过可能与肿瘤稳态和生长相关的条件诱导的云母/B表达可以在针对肿瘤的免疫应答中发挥作用。
Human MHC class I-related molecules, MICA and MICB, are stress-induced antigens that are recognized by a subset of gamma delta T cells expressing the variable region Vdelta1. This functional association has been found to be limited to intestinal epithelium, where these T cells are prevalent and where MICA and, presumably, MICB are mainly expressed. However, increased frequencies of Vdelta1 gamma delta T cells have been observed in various epithelial tumors; moreover, MICA/B are expressed on diverse cultured epithelial tumor cells. With freshly isolated tumor specimens, expression of MICA/B was documented in many, but not all, carcinomas of the lung, breast, kidney, ovary, prostate, and colon. In tumors that were positive for MICA/B, the frequencies of Vdelta1 gamma delta T cells were significantly higher than in those that were negative. Vdelta1 gamma delta T cell lines and clones derived from different tumors recognized MICA/B on autologous and heterologous tumor cells. In accord with previous evidence, no constraints were observed in these interactions, such as those imposed by specific peptide ligands. Thus, MICA/B are tumor-associated antigens that can be recognized, in an apparently unconditional manner, by a subset of tumor-infiltrating gamma delta T cells. These results raise the possibility that an induced expression of MICA/B, by conditions that may be related to tumor homeostasis and growth, could play a role in immune responses against tumors.