IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity
IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity
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DOI：
10.1038/35074122
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发表时间：
2001-04-26
期刊：
影响因子：
64.8
通讯作者：
Schreiber, RD
中科院分区：
文献类型：
--
作者：
Shankaran, V;Ikeda, H;Schreiber, RD
淋巴细胞最初被认为是形成“癌症免疫监视”过程的基础，该过程保护免疫活性宿主免受原发性肿瘤发展的影响（1，2），但当在无胸腺裸鼠和同基因野生型小鼠之间没有发现原发性肿瘤发展的差异时，这一想法在很大程度上被放弃（3-5）。然而，随后的观察结果表明，裸鼠并不完全缺乏功能性T细胞（6，7），免疫系统的两种成分-IFN γ（8，9）和穿孔素（10-12）-有助于防止小鼠肿瘤形成，这导致了对免疫应答的肿瘤抑制作用的重新关注。在这里，我们表明，淋巴细胞和IFN-γ合作，以防止发展的致癌物质诱导的肉瘤和自发性上皮癌，也选择肿瘤细胞的免疫原性降低。因此，免疫反应作为一种有效的外源性肿瘤抑制系统发挥作用。然而，这一过程也导致肿瘤细胞的免疫选择，这些细胞更能够在免疫活性宿主中存活，这解释了免疫完整个体中肿瘤形成的明显矛盾。
Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development(1,2), but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice(3-5). However, subsequent observations that nude mice do not completely lack functional T cells(6,7) and that two components of the immune system-IFN gamma (8,9) and perforin(10-12)-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFN gamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.