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  • Title: Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion.
    Author: Montes CL, Chapoval AI, Nelson J, Orhue V, Zhang X, Schulze DH, Strome SE, Gastman BR.
    Journal: Cancer Res; 2008 Feb 01; 68(3):870-9. PubMed ID: 18245489.
    Abstract:
    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.
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