title: Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion.
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.
authors.affiliation: Department of Otorhinolaryngology, University of Maryland School of Medicine, Baltimore, Maryland 21202, USA.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Montes
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Chapoval
authors.forename: Jonas
authors.initials: J
authors.lastname: Nelson
authors.forename: Vbenosa
authors.initials: V
authors.lastname: Orhue
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Dan H
authors.initials: DH
authors.lastname: Schulze
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.forename: Brian R
authors.initials: BR
authors.lastname: Gastman
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000276:immunology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000276:immunology; D004249:DNA Damage / Q000276:immunology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D018797:Cell Cycle Proteins