Möhler T, Willhauck M, Scheibenbogen C, Pawlita M, Bludau H, Brossart P, Hunstein W, Keilholz U
Department of Internal Medicine V, University of Heidelberg, Germany.
Melanoma Res. 1995 Apr;5(2):129-32. doi: 10.1097/00008390-199504000-00010.
Restriction of the T cell receptor repertoire suggesting ongoing specific immune mechanisms has recently been described in melanoma tissue by several groups of investigators. The functional relevance for immunotherapy of melanoma, however, has not been established. We studied the T cell receptor repertoire in two melanoma metastases of a patient with a mixed response to immunotherapy. Expression of T cell receptor V beta regions was determined by subgroup-specific semiquantitative RNA polymerase chain reaction (PCR). In the regressing skin lesion a restricted expression of the T cell receptor repertoire and overexpression of three V beta subgroup genes was found; no restriction was present in the simultaneously progressing skin lesion of the same patient, compared with peripheral blood lymphocytes. Comparison of T cell receptor V beta gene expression in two metastatic lesions of a patient with simultaneously growing skin metastases, who did not receive immunotherapy, revealed only minor differences. These observations show for the first time an association between restricted T cell receptor repertoire and responsiveness of melanoma to immunotherapy and suggest a role of T cells using the overexpressed V beta genes for the cytokine-induced tumour regression.
最近，几组研究人员在黑色素瘤组织中描述了T细胞受体库的限制，这表明存在持续的特异性免疫机制。然而，黑色素瘤免疫治疗的功能相关性尚未确立。我们研究了一名对免疫治疗有混合反应的患者的两个黑色素瘤转移灶中的T细胞受体库。通过亚组特异性半定量RNA聚合酶链反应（PCR）测定T细胞受体Vβ区的表达。在消退的皮肤病变中，发现T细胞受体库的表达受限，并且三个Vβ亚组基因过表达；与外周血淋巴细胞相比，同一患者同时进展的皮肤病变中未发现限制。对一名未接受免疫治疗且皮肤转移灶同时生长的患者的两个转移灶中的T细胞受体Vβ基因表达进行比较，仅发现微小差异。这些观察结果首次表明T细胞受体库的限制与黑色素瘤对免疫治疗的反应性之间存在关联，并提示使用过表达的Vβ基因的T细胞在细胞因子诱导的肿瘤消退中发挥作用。
