Telomere Science Library

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about the Nobel-Prize Winning Science of Telomere Biology

Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion

Carolina L. Montes, Andrei I. Chapoval, Jonas Nelson, Vbenosa Orhue, Xiaoyu Zhang, Dan H. Schulze, Scott E. Strome, and Brian R. Gastman

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. [Cancer Res 2008;68(3):870-9]

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