Ito K, Fetten J, Khalili H, Hajdu S, Busch E, Pergolizzi R, Vinciguerra V, Chang M D
Department of Medicine, North Shore University Hospital-New York University Medical College, Manhasset, USA.
Mol Med. 1997 Dec;3(12):836-51.
Substantial evidence has suggested that T cells play an important role in antitumor immunity. T cells with cytotoxic activity against tumors have been isolated from in vitro culture of tumor-infiltrated lymphocytes of cancer patients. In addition, clonal expansions of T cells have been identified in lesions of tumors by using a PCR-based CDR3 analysis of T cell receptors (TCR). Since the CDR3 region of the T cell receptor directly interacts with the antigen-MHC complex and is thus highly polymorphic, a dominant CDR3 length in a particular TCR V beta population will indicate the clonal expansion of a specific T cell clone. Utilizing this technique, we have analyzed the T cell repertoire in lymph nodes (LNs) and peripheral blood of 20 breast cancer patients. Our results show that in most cases, peripheral blood mononuclear cells (PB-MCs) and LN express dominant CD8+ T cell clones in different V beta gene families, and the number of dominant clones is higher in PBMC than in the LN. Furthermore, in 7 out of 16 patients' lymph nodes, there is a dominant V beta 18 T cell clonal expansion in the CD8+ T cell subset. The frequency of an oligoclonal expansion of V beta 18 CD8+ T cells in non-breast cancer lymph nodes is 1 out of 9, but no obvious motif in the CDR3 region of V beta 18 TCR can be identified. The prevalence of the clonal dominance found in breast cancer is discussed in the context of a possible tumor-related antigen stimulation.
大量证据表明，T细胞在抗肿瘤免疫中发挥着重要作用。已从癌症患者肿瘤浸润淋巴细胞的体外培养物中分离出对肿瘤具有细胞毒性活性的T细胞。此外，通过基于PCR的T细胞受体（TCR）CDR3分析，在肿瘤病变中已鉴定出T细胞的克隆扩增。由于T细胞受体的CDR3区域直接与抗原-MHC复合物相互作用，因此具有高度多态性，特定TCR Vβ群体中占主导地位的CDR3长度将表明特定T细胞克隆的克隆扩增。利用这项技术，我们分析了20例乳腺癌患者淋巴结（LN）和外周血中的T细胞库。我们的结果表明，在大多数情况下，外周血单个核细胞（PB-MCs）和LN在不同的Vβ基因家族中表达占主导地位的CD8+T细胞克隆，并且PBMC中主导克隆的数量高于LN。此外，在16例患者的淋巴结中有7例，CD8+T细胞亚群中存在占主导地位的Vβ18 T细胞克隆扩增。非乳腺癌淋巴结中Vβ18 CD8+T细胞寡克隆扩增的频率为9例中有1例，但在Vβ18 TCR的CDR3区域未发现明显基序。在可能的肿瘤相关抗原刺激的背景下讨论了在乳腺癌中发现的克隆优势的普遍性。
