Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion.
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.
Montes
Carolina L
CL
Department of Otorhinolaryngology, University of Maryland School of Medicine, Baltimore, Maryland 21202, USA.
Chapoval
Andrei I
AI
Nelson
Jonas
J
Orhue
Vbenosa
V
Zhang
Xiaoyu
X
Schulze
Dan H
DH
Strome
Scott E
SE
Gastman
Brian R
BR
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*
D018797:Cell Cycle Proteins