Topalian S L, Hom S S, Kawakami Y, Mancini M, Schwartzentruber D J, Zakut R, Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunother (1991). 1992 Oct;12(3):203-6. doi: 10.1097/00002371-199210000-00013.
We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor-infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2- melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines.
我们已经确定,黑色素瘤表达共享肿瘤抗原(Ags),如果这些抗原在自身MHC分子的背景下呈递,就能够被T细胞识别。对来自6名黑色素瘤患者的肿瘤浸润淋巴细胞(TILs)进行检测,观察其对大量代表各种组织类型的HLA匹配或不匹配靶标的裂解情况。裂解作用对与TILs共享至少一种HLA-A、-B或-C抗原的同种异体黑色素瘤具有特异性,并证明了肿瘤抗原的共同表达。当用TILs的细胞因子分泌来指示特异性抗原识别时,也获得了类似的结果。将HLA-A2.1基因转染到HLA-A2阴性的黑色素瘤细胞系中,使其对受HLA-A2限制的黑色素瘤TILs的裂解敏感,这表明不同HLA类型的患者中存在共同的肿瘤抗原表达。这些发现对于开发广泛适用的癌症免疫疗法(如疫苗)具有重要意义。