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人肿瘤浸润淋巴细胞对黑色素瘤共同抗原的识别。

Recognition of shared melanoma antigens by human tumor-infiltrating lymphocytes.

作者信息

Topalian S L, Hom S S, Kawakami Y, Mancini M, Schwartzentruber D J, Zakut R, Rosenberg S A

机构信息

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

出版信息

J Immunother (1991). 1992 Oct;12(3):203-6. doi: 10.1097/00002371-199210000-00013.

Abstract

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.

摘要

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。

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