Tumor-induced senescent T cells with suppressor function: A potential form of tumor immune evasion
Tumor-induced senescent T cells with suppressor function: A potential form of tumor immune evasion
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DOI：
10.1158/0008-5472.can-07-2282
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发表时间：
2008-02-01
期刊：
影响因子：
11.2
通讯作者：
Gastman, Brian R.
中科院分区：
文献类型：
--
作者：
Montes, Carolina L.;Chapoval, Andrei I.;Gastman, Brian R.
据报道，某些癌症患者的衰老和抑制性 T 细胞有所增加，并且是不良预后指标。基于这些 T 细胞与不良结果的关联，我们假设肿瘤会诱导 T 细胞衰老，从而对抗肿瘤免疫产生负面影响。在本报告中，我们表明，来自健康捐献者的人类 T 细胞在肿瘤与 T 细胞比例较低的情况下仅与肿瘤一起孵育 6 小时，就会出现衰老样表型，其特征是 CD27 和 CD28 表达丧失以及端粒缩短。肿瘤诱导的 T 细胞衰老是由可溶性因子诱导的，并引发衰老相关分子（如 p53、p21 和 p16）表达增加。重要的是，这些 T 细胞不仅表型发生改变，而且功能也发生改变，因为它们可以抑制应答 T 细胞的增殖。这种抑制需要细胞间接触，并由衰老的 CD4(+) 和 CD8(+) 亚群介导，这与经典描述的天然 T 调节细胞不同。我们的观察结果支持了这样一个新概念：肿瘤可以诱导具有抑制功能的衰老 T 细胞，并可能影响癌症的诊断和治疗。
Senescent and suppressor T cells are reported to be increased in select patients with cancer and are poor prognostic indicators. Based on the association of these T cells and poor outcomes, we hypothesized that tumors induce senescence in T cells, which negatively effects antitumor immunity. In this report, we show that human T cells from healthy donors incubated with tumor for only 6 h at a low tumor to T-cell ratio undergo a senescence-like phenotype, characterized by the loss of CD27 and CD28 expression and telomere shortening. Tumor-induced senescence of T cells is induced by soluble factors and triggers increases in expression of senescence-associated molecules such as p53, p21, and p16. Importantly, these T cells are not only phenotypically altered, but also functionally altered as they can suppress the proliferation of responder T cells. This suppression requires cell-to-cell contact and is mediated by senescent CD4(+) and CD8(+) subpopulations, which are distinct from classically described natural T regulatory cells. Our observations support the novel concept that tumor can induce senescent T cells with suppressor function and may effect both the diagnosis and treatment of cancer.