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Interferon‐γ‐producing Tumor Induces Host Tumor‐specific T Cell Responses

机译:产生γ干扰素的肿瘤诱导宿主肿瘤特异性T细胞反应

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摘要

We investigated the mechanism of host immune responses against two interferon‐γ (IFN‐γ) gene‐transduced tumors, plasmacytoma MOPC104E(Muγ) and mammary cancer SC115(Kγ), which originally had weak immunogenicity. Both IFN‐γ‐producing tumor cells had reduced tumorigenicity and were rejected by syngeneic mice. The rejection was completely blocked by in vivo treatment with anti‐CD8 or anti‐IFN‐γ monoclonal antibodies. While anti‐CD4 monoclonal antibody also blocked the rejection of SC115(Kγ), it enhanced the initial tumor growth of MOPC104E(Muγ). Specific protection against subsequent challenge with the respective parental tumor cells was demonstrated in mice which rejected the IFN‐γ‐producing tumor cells. Cultured lymphocytes derived from immunized mouse spleens had cytotoxic T cell activity against parental tumor cells, as well as against cells that produced IFN‐γ, These findings indicate that the antitumor effects are mediated by cytotoxic T cells and, partly, by helper T cells, and that locally secreted IFN‐γ plays an important role in generating these effector cells.
机译:我们研究了针对两种干扰素-γ(IFN-γ)基因转导的肿瘤,原本免疫原性较弱的浆细胞瘤MOPC104E(Muγ)和乳癌SC115(Kγ)的宿主免疫应答机制。两种产生IFN-γ的肿瘤细胞均降低了致瘤性,并被同系小鼠排斥。通过抗CD8或抗IFN-γ单克隆抗体的体内治疗可以完全阻止排斥反应。抗CD4单克隆抗体也可以阻止SC115(Kγ)的排斥,但它可以增强MOPC104E(Muγ)的初始肿瘤生长。在拒绝产生IFN-γ的肿瘤细胞的小鼠中证明了针对各个亲代肿瘤细胞的后续攻击的特异性保护。来自免疫小鼠脾脏的培养淋巴细胞具有针对亲代肿瘤细胞以及产生IFN-γ的细胞的细胞毒性T细胞活性。这些发现表明,抗肿瘤作用是由细胞毒性T细胞以及部分由辅助T细胞介导的,局部分泌的IFN-γ在产生这些效应细胞中起着重要作用。

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