Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion

CL Montes, AI Chapoval, J Nelson, V Orhue, X Zhang… - Cancer research, 2008 - AACR
CL Montes, AI Chapoval, J Nelson, V Orhue, X Zhang, DH Schulze, SE Strome, BR Gastman
Cancer research, 2008AACR
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 …
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. [Cancer Res 2008;68(3):870–9]
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