Senescencia de celulas T inducida por tumores

CAROLINA MONTES

La Falda

Congreso; LVI Reunión Anual de la Sociedad Argentina de Inmunología; 2008

Sociedad Argentina de Inmunologia

   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 impacts anti-tumor immunity.  In this report we demonstrate that human T cells from healthy donors incubated with tumor for only 6 hours at a low Tumor:T cell ratio undergo a senescence like phenotype, characterized by the loss of CD27 and CD28 expression and telomere shortening.   Tumor induced senescence (TIS) 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 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 impact both the diagnosis and treatment of cancer.