TY - JOUR
T1 - Tumor-induced senescent T cells with suppressor function
T2 - A potential form of tumor immune evasion
AU - Montes, Carolina L.
AU - Chapoval, Andrei I.
AU - Nelson, Jonas
AU - Orhue, Vbenosa
AU - Zhang, Xiaoyu
AU - Schulze, Dan H.
AU - Strome, Scott E.
AU - Gastman, Brian R.
PY - 2008/2/1
Y1 - 2008/2/1
N2 - 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.
AB - 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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U2 - 10.1158/0008-5472.CAN-07-2282
DO - 10.1158/0008-5472.CAN-07-2282
M3 - Article
C2 - 18245489
AN - SCOPUS:38849181710
VL - 68
SP - 870
EP - 879
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 3
ER -