Okada Y, Yahata G, Takeuchi S, Seidoh T, Tanaka K
Department of Obstetrics and Gynecology, Niigata University School of Medicine.
Jpn J Cancer Res. 1989 Mar;80(3):249-56. doi: 10.1111/j.1349-7006.1989.tb02301.x.
Tumor-infiltrating lymphocytes (TIL) from six gynecologic malignant tumors (two uterine cervical cancers, two ovarian serous cystadenocarcinomas, and two uterine corpus cancers), cultured in the presence of recombinant interleukin 2, were assayed for their cytotoxic activities against various fresh tumor cells including autologous tumors. A clear correlation between phenotype and cytotoxic activity of TIL was observed. Four of six TIL preparations exhibited strong cytotoxic activity against autologous fresh tumor target cells, and were all CD8+. In contrast, cytotoxic activity was not detected in any of the CD4+ TIL preparations. The cytotoxic activities of the CD8+ TIL preparations were highly specific; only autologous fresh tumor cells were lysed. This result is consistent with the notion that TIL are of a different cell lineage from lymphokine-activated killer cells which are antigen-nonspecific and CD8-. Instead, TIL appear to be of cytotoxic T cell lineage that is highly antigen-specific and CD8+. To explore the potential for clinical use, we have attempted to augment the cytotoxic activities of these CD8+ TIL by treatment of the target tumor cells with gamma interferon (IFN) in vitro, hoping that elevated expression of MHC class I gene products on the cell surface would enhance their recognition. It was observed that brief treatment of freshly prepared tumor cells in vitro with gamma-IFN resulted in augmentation of the expression of MHC class I gene products, and the treated tumor cells were more susceptible to lysis by TIL than untreated cells.
对来自六种妇科恶性肿瘤（两种子宫颈癌、两种卵巢浆液性囊腺癌和两种子宫内膜癌）的肿瘤浸润淋巴细胞（TIL）在重组白细胞介素2存在的情况下进行培养，然后检测它们对包括自体肿瘤在内的各种新鲜肿瘤细胞的细胞毒性活性。观察到TIL的表型与细胞毒性活性之间存在明显的相关性。六种TIL制剂中有四种对自体新鲜肿瘤靶细胞表现出强烈的细胞毒性活性，并且均为CD8+。相比之下，在任何CD4+ TIL制剂中均未检测到细胞毒性活性。CD8+ TIL制剂的细胞毒性活性具有高度特异性；仅自体新鲜肿瘤细胞被裂解。该结果与以下观点一致，即TIL与淋巴因子激活的杀伤细胞属于不同的细胞谱系，后者是抗原非特异性的且为CD8-。相反，TIL似乎属于细胞毒性T细胞谱系，具有高度抗原特异性且为CD8+。为了探索临床应用的潜力，我们试图通过在体外使用γ干扰素（IFN）处理靶肿瘤细胞来增强这些CD8+ TIL的细胞毒性活性，希望细胞表面MHC I类基因产物的表达升高能够增强它们的识别能力。观察到在体外使用γ干扰素对新鲜制备的肿瘤细胞进行短暂处理会导致MHC I类基因产物的表达增加，并且与未处理的细胞相比，经处理的肿瘤细胞更容易被TIL裂解。
