Willhauck Martina, Scheibenbogen Carmen, Pawlita Michael, Möhler Thomas, Thiel Eckhard, Keilholz Ulrich
Medizinische Klinik und Poliklinik V, Hospitalstrasse 3, 69115 Heidelberg, Germany.
Cancer Res. 2003 Jul 1;63(13):3483-5.
One major rationale for using interleukin-2 and IFN-alpha in cancer immunotherapy is to activate tumor-specific T cells at the tumor site. To study the in situ T-cell response, we determined the T-cell receptor (TCR) repertoire in six melanoma metastases regressing after cytokine treatment obtained from five patients. Sequence analysis of overexpressed TCR beta-chain variable regions revealed the presence of clonally expanded T cells and also of T cells with highly homologous complementarity determining regions 3 in all five patients. This finding indicates that the T-cell response in regressing melanoma lesions is dominated by T cells directed toward a limited number of epitopes and that epitope-specific T cells frequently use a highly restricted TCR repertoire.
在癌症免疫治疗中使用白细胞介素-2和α干扰素的一个主要基本原理是激活肿瘤部位的肿瘤特异性T细胞。为了研究原位T细胞反应，我们测定了从5名患者身上获取的6个经细胞因子治疗后消退的黑色素瘤转移灶中的T细胞受体（TCR）库。对过表达的TCRβ链可变区进行序列分析发现，所有5名患者中均存在克隆性扩增的T细胞以及互补决定区3高度同源的T细胞。这一发现表明，消退的黑色素瘤病灶中的T细胞反应主要由针对有限数量表位的T细胞主导，且表位特异性T细胞经常使用高度受限的TCR库。
