El Hage Faten, Vergnon Isabelle, Grunenwald Dominique, Soria Jean Charles, Chouaib Salem, Mami-Chouaib Fathia
Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, F-94 805 Villejuif, France.
Oncol Rep. 2005 Sep;14(3):763-9.
We have identified an antigen recognized on a large cell carcinoma of the lung by tumor-specific cytotoxic T lymphocytes (CTL). The antigenic peptide is encoded by a mutated alpha-actinin-4 gene and presented by human leukocyte antigen (HLA)-A2. Using HLA-A2-peptide tetramers, we have derived from patient peripheral blood lymphocytes (PBL) and autologous tumor infiltrating lymphocytes (TIL) several mutated alpha-actinin-4-specific T cell clones. These clones displayed similar tetramer staining but distinct T cell receptor (TCR) usage and antitumor reactivity. Indeed, TIL clones lysed more efficiently the autologous tumor cells and released higher cytokine levels than PBL clones. Importantly, treatment of cancer cells with interferon-gamma enhanced their susceptibility to PBL clone-mediated lysis correlated with increase in HLA-class I expression. The present findings provide evidence that an immune T cell response took place in a lung cancer patient with favorable clinical evolution and suggest that CTL, recognizing a truly tumor-specific antigen, may contribute to controlling the tumor.
我们已经鉴定出一种可被肿瘤特异性细胞毒性T淋巴细胞（CTL）识别的肺大细胞癌抗原。该抗原肽由突变的α-辅肌动蛋白-4基因编码，并由人类白细胞抗原（HLA）-A2呈递。利用HLA-A2-肽四聚体，我们从患者外周血淋巴细胞（PBL）和自体肿瘤浸润淋巴细胞（TIL）中获得了多个突变α-辅肌动蛋白-4特异性T细胞克隆。这些克隆显示出相似的四聚体染色，但T细胞受体（TCR）使用情况和抗肿瘤反应不同。事实上，与PBL克隆相比，TIL克隆能更有效地裂解自体肿瘤细胞并释放更高水平的细胞因子。重要的是，用干扰素-γ处理癌细胞可增强其对PBL克隆介导的裂解的敏感性，这与HLA-I类表达的增加相关。目前的研究结果提供了证据，表明在一名临床病程良好的肺癌患者中发生了免疫T细胞反应，并表明识别真正肿瘤特异性抗原的CTL可能有助于控制肿瘤。
