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, Brian R. Gastman

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)870-879
Number of pages10
JournalCancer Research
Volume68
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Montes, C. L., Chapoval, A. I., Nelson, J., Orhue, V., Zhang, X., Schulze, D. H., Strome, S. E., & Gastman, B. R. (2008). Tumor-induced senescent T cells with suppressor function: A potential form of tumor immune evasion. Cancer Research, 68(3), 870-879. https://doi.org/10.1158/0008-5472.CAN-07-2282