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

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

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Tumor Escape
T-Lymphocytes
Neoplasms
Telomere Shortening
Regulatory T-Lymphocytes
Immunity
Tissue Donors
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tumor-induced senescent T cells with suppressor function : A potential form of tumor immune evasion. / Montes, Carolina L.; Chapoval, Andrei; Nelson, Jonas; Orhue, Vbenosa; Zhang, Xiaoyu; Schulze, Dan H.; Strome, Scott E.; Gastman, Brian R.

In: Cancer Research, Vol. 68, No. 3, 01.02.2008, p. 870-879.

Research output: Contribution to journalArticle

Montes, CL, Chapoval, A, Nelson, J, Orhue, V, Zhang, X, Schulze, DH, Strome, SE & Gastman, BR 2008, 'Tumor-induced senescent T cells with suppressor function: A potential form of tumor immune evasion', Cancer Research, vol. 68, no. 3, pp. 870-879. https://doi.org/10.1158/0008-5472.CAN-07-2282
Montes, Carolina L. ; Chapoval, Andrei ; Nelson, Jonas ; Orhue, Vbenosa ; Zhang, Xiaoyu ; Schulze, Dan H. ; Strome, Scott E. ; Gastman, Brian R. / Tumor-induced senescent T cells with suppressor function : A potential form of tumor immune evasion. In: Cancer Research. 2008 ; Vol. 68, No. 3. pp. 870-879.
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