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

• Autores: Montes, Carolina Lucia; Chapoval, Andrei I.; Nelson, Jonas; Orhue, Vbenosa; Zhang, Xiaoyu; Schulze, Dan H.; Strome, Scott E.; Gastman, Brian R.
• Año de publicación: 2008
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Senescence; T cell; Tumor; Immunology
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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. ©2008 American Association for Cancer Research.
Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Chapoval, Andrei I.. University of Maryland; Estados Unidos
Fil: Nelson, Jonas. University of Maryland; Estados Unidos
Fil: Orhue, Vbenosa. University of Maryland; Estados Unidos
Fil: Zhang, Xiaoyu. University of Maryland; Estados Unidos
Fil: Schulze, Dan H.. University of Maryland; Estados Unidos
Fil: Strome, Scott E.. University of Maryland; Estados Unidos
Fil: Gastman, Brian R.. University of Maryland; Estados Unidos