Division of Oncology, Departments of Medicine, Pathology and Molecular Imaging, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cancer Cell. 2010 Nov 16;18(5):485-98. doi: 10.1016/j.ccr.2010.10.002. Epub 2010 Oct 28.
Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of tumorigenesis, but their role in oncogene inactivation-mediated tumor regression is unclear. Here, we show that an intact immune system, specifically CD4(+) T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained tumor regression. Hence, CD4(+) T cells are required for the remodeling of the tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction.
癌基因成瘾被认为是自主发生的。免疫效应物被牵连到肿瘤发生的启动和抑制中，但它们在癌基因失活介导的肿瘤消退中的作用尚不清楚。在这里，我们表明，在 T 细胞急性淋巴细胞白血病和前 B 细胞白血病的小鼠模型中，分别失活 MYC 或 BCR-ABL 癌基因后，完整的免疫系统（特别是 CD4+T 细胞）对于诱导细胞衰老、血管生成关闭以及趋化因子表达导致持续的肿瘤消退是必需的。此外，敲除血小板反应蛋白的免疫效应物未能诱导持续的肿瘤消退。因此，CD4+T 细胞需要通过表达趋化因子（如血小板反应蛋白）重塑肿瘤微环境，以引发癌基因成瘾。
