Halapi E, Yamamoto Y, Juhlin C, Jeddi-Tehrani M, Grunewald J, Andersson R, Hising C, Masucci G, Mellstedt H, Kiessling R
Department of Immunology, Karolinska Institutet, Stockholm, Sweden.
Cancer Immunol Immunother. 1993;36(3):191-7. doi: 10.1007/BF01741091.
Tumour-infiltrating lymphocytes (TIL) are often observed in human tumours and their presence has been correlated with a better prognosis. It has been suggested that TIL are enriched for tumour-specific cytotoxic cells, and TIL activated and expanded in vitro by interleukin-2 (IL-2) are currently used in the therapy of human cancer. We have studied the T cell repertoire in IL-2-expanded TIL cells from patients with ovarian and renal carcinoma using T-cell-receptor-V-beta-specific monoclonal antibodies and a polymerase-chain-reaction-based Southern blot technique for analysis of J-beta usage. In TIL lines derived from three of nine patients with ovarian carcinomas and from two of eight patients with renal carcinomas, selective usage of the V-beta 6 or V-beta 5 T-cell receptor gene products was found. The majority of the cells were CD4+, with up to 40% of the T cells utilizing the same V-beta gene. T-cell lines derived from peripheral blood lymphocytes from patients or healthy donors contained normal levels of V-beta subsets. Only moderate levels of V-beta 6+ T cells were detected from freshly isolated TIL and the increase of this subpopulation appeared as a result of in vitro culture. The level of clonal restriction, as measured by the usage of J-beta gene segments within the V-beta 5 or V-beta 6 families, was analysed using a recently developed technique based on the polymerase chain reaction. Evidence for restricted J-beta usage was detected only in TIL expanded in vitro, while this was not the case in freshly isolated tumour-derived lymphocytes or T cell lines obtained from peripheral blood lymphocytes. The presence of a population with biased T cell receptor expression in cells derived from tumour tissue could be explained by their activation in vivo as a result of contact with tumour antigens and should be taken into consideration when discussing the therapeutic efficiency of IL-2-expanded TIL.
肿瘤浸润淋巴细胞（TIL）在人类肿瘤中经常可见，其存在与较好的预后相关。有人提出，TIL富含肿瘤特异性细胞毒性细胞，目前通过白细胞介素-2（IL-2）在体外激活并扩增的TIL被用于人类癌症的治疗。我们使用T细胞受体V-β特异性单克隆抗体和基于聚合酶链反应的Southern印迹技术来分析J-β的使用情况，研究了卵巢癌和肾癌患者经IL-2扩增的TIL细胞中的T细胞库。在9例卵巢癌患者中的3例以及8例肾癌患者中的2例所衍生的TIL系中，发现了V-β6或V-β5 T细胞受体基因产物的选择性使用。大多数细胞为CD4 +，高达40%的T细胞利用相同的V-β基因。源自患者或健康供体外周血淋巴细胞的T细胞系含有正常水平的V-β亚群。从新鲜分离的TIL中仅检测到中等水平的V-β6 + T细胞，该亚群的增加似乎是体外培养的结果。使用基于聚合酶链反应的最新技术分析了通过V-β5或V-β6家族内J-β基因片段的使用来衡量的克隆限制水平。仅在体外扩增的TIL中检测到J-β使用受限的证据，而在新鲜分离的肿瘤来源淋巴细胞或从外周血淋巴细胞获得的T细胞系中则并非如此。肿瘤组织来源的细胞中存在T细胞受体表达有偏向性的群体，可以解释为它们在体内因与肿瘤抗原接触而被激活，在讨论IL-2扩增的TIL的治疗效果时应予以考虑。
