Willhauck M, Möhler T, Scheibenbogen C, Pawlita M, Brossart P, Schmier J W, Keilholz U
Department of Internal Medicine V, University of Heidelberg, Hospitalstrasse 3, 69115 Heidelberg, Germany.
Clin Cancer Res. 1996 Apr;2(4):767-72.
Limited T-cell receptor (TCR) repertoire of tumor-infiltrating lymphocytes has been found in melanoma metastases and spontaneously regressing melanoma. Immunotherapy with INF-alpha/interleukin 2 can induce tumor regression in a proportion of patients with metastatic melanoma. We analyzed the gene expression of the TCR-beta variable (Vbeta) region of tumor-infiltrating lymphocytes from 16 melanoma metastases by subgroup-specific semiquantitative RNA PCR to investigate the influence of immunotherapy on the TCR pattern. In five progressing metastases before or after immunotherapy, no overexpression of Vbeta gene families was detectable, whereas in seven of seven metastases responding to IFN-alpha/interleukin 2 one to four Vbeta gene families were overexpressed. Preferential usage of certain Vbeta gene subgroups in patients sharing the same HLA class I molecules suggests a T-cell response to dominant public epitopes. Analysis of multiple specimens from the same patients gives evidence that this strong oligoclonal T-cell selection is induced or at least augmented by immunotherapy, supporting the functional relevance of this finding.
在黑色素瘤转移灶和自发消退的黑色素瘤中发现肿瘤浸润淋巴细胞的T细胞受体（TCR）库有限。α干扰素/白细胞介素2免疫疗法可使一部分转移性黑色素瘤患者出现肿瘤消退。我们通过亚组特异性半定量RNA聚合酶链反应分析了16例黑色素瘤转移灶中肿瘤浸润淋巴细胞TCR-β可变（Vβ）区的基因表达，以研究免疫疗法对TCR模式的影响。在免疫疗法前后的5个进展性转移灶中，未检测到Vβ基因家族的过表达，而在7个对α干扰素/白细胞介素2有反应的转移灶中的7个中，1至4个Vβ基因家族过表达。在共享相同I类人类白细胞抗原分子的患者中，某些Vβ基因亚组的优先使用提示T细胞对显性公共表位有反应。对同一患者的多个标本进行分析表明，这种强烈的寡克隆T细胞选择是由免疫疗法诱导的，或至少因免疫疗法而增强，这支持了这一发现的功能相关性。
