Tumor induced senescence T-lymphocytes (TIST): phenotype and functional characterization

RAMELLO MC; ACOSTA RODRIGUEZ EV; MONTES CL

mar del Plata Argentina

Congreso; LVII Reunión Anual de la Sociedad Argentina de Inmunología; 2009

Sociedad Aregentina de inmunologia

Senescent T cells are increased in patients with cancer and are a poor prognostic indicator. Previously we demonstrated that a high percentage of human T cells from healthy donors incubated with different tumor cell lines for short time at a 1:1 Tumor /T cell ratio and then cultured for 7 days, undergo senescence as judged by the incremental loss of CD27 and CD28  expression and telomere shortening. Herein we show that CD4+ and CD8+ T cells were equally susceptible to undergo senescence after co-incubation with Tumor cell lines. We evaluated the expression of molecules associated with activation, co-stimulation and regulation in TIST lymphocytes. We observed that a 70%±11 of CD8+CD28-CD27- TIST cells expressed CD45 RA while only 25%±13 of CD4+CD28-CD27- expressed this marker. Neither CD4+ nor CD8+ TIST lymphocytes expressed CD62L. CD4+ and CD8+ TIST cells exhibited higher percentage of PD-1+ cells than control (T cells without tumor co-incubation). Evaluation of INF gamma expression after PMA/iono stimulation showed a higher percentage of INF gamma+ cells in CD4+ and CD8+ TIST lymphocytes than in control T lymphocytes. These results demonstrated that TIST lymphocytes show a phenotype of experienced T cells commonly increased in patient with different cancer and chronic infections.