Velotti F, Chopin D, Gil-Diez S, Maille P, Abbou C C, Kourilsky P, Even J
Groupe d'Etude des Tumeurs Urologiques (GETU), Formation associée Claude Bernard, Université Paris XII, Hôpital Henri Mondor, Créteil, France.
J Immunother. 1997 Nov;20(6):470-8. doi: 10.1097/00002371-199711000-00007.
The immune system has been implicated in the control of bladder tumor growth. To evaluate the clonality of bladder tumor-infiltrating T lymphocytes (TILs) in vivo, we studied the T-cell antigen receptor (TCR) repertoire in tumor biopsy specimens from 10 patients with transitional-cell carcinoma (TCC) of the bladder. Nine patients had a primary tumor, and one had a multifocal disease, consisting of two bladder tumors and three bilateral upper urinary tract sites of involvement. The following specimens from the nine patients with a primary tumor also were analyzed: a recurrent tumor from four patients, a metastatic lymph node from one patient, and peripheral blood from five patients. We used a high-resolution polymerase chain reaction (PCR) method to determine CDR3 (complementarity-determining region 3) size lengths of TCR beta-chain transcripts. Oligoclonal T-cell expansion was identified in all specimens, with a larger number of expanded clones in the tumors than in peripheral blood. Expanded clones were identified in several beta-chain variable region (BV) subfamilies and varied from one patient to the next and also in different specimens from the same patient. However, a number of clones with the same VJ combination and the same CDR3 size were identified in a given patient (in specimens collected either simultaneously or at different times), suggesting homogeneity in the immunogenic environment. Clonal T-cell expansion in patients with bladder cancer may reflect prolonged exposure of T lymphocytes to tumor antigens. Our findings provide a basis for functional studies to elucidate T lymphocyte-bladder tumor cell interactions.
免疫系统与膀胱肿瘤生长的控制有关。为了评估体内膀胱肿瘤浸润性T淋巴细胞（TILs）的克隆性，我们研究了10例膀胱移行细胞癌（TCC）患者肿瘤活检标本中的T细胞抗原受体（TCR）库。9例患者患有原发性肿瘤，1例患有多灶性疾病，包括两个膀胱肿瘤和三个双侧上尿路受累部位。还分析了9例原发性肿瘤患者的以下标本：4例患者的复发性肿瘤、1例患者的转移性淋巴结和5例患者的外周血。我们使用高分辨率聚合酶链反应（PCR）方法来确定TCRβ链转录本的CDR3（互补决定区3）大小长度。在所有标本中均鉴定出寡克隆T细胞扩增，肿瘤中扩增的克隆数量多于外周血。在几个β链可变区（BV）亚家族中鉴定出扩增的克隆，不同患者之间以及同一患者的不同标本中均有所不同。然而，在给定患者中（在同时或不同时间收集的标本中）鉴定出一些具有相同VJ组合和相同CDR3大小的克隆，这表明免疫原性环境具有同质性。膀胱癌患者中的克隆性T细胞扩增可能反映了T淋巴细胞长期暴露于肿瘤抗原。我们的发现为阐明T淋巴细胞与膀胱肿瘤细胞相互作用的功能研究提供了基础。
