Tumor induced senescent T cells (TIST) promote the production of pro-inflammatory cytokines and angiogenic factors by human monocytes through a cell to cell contact mechanism

RAMELLO MC; TOSELLO BOARI J; CANALE F; ACOSTA RODRIGUEZ EV; MONTES CL

Congreso; First Argentinean Spring Course in Advance Immunology and LXI Reunión Anual de la Sociedad Argentina de Inmunología.; 2013

We demonstrated that a high percentage of human CD4+ or CD8+ T cells from healthy donors incubated with different tumor cell lines in vitro and then cultured for 7 days lose the expression of CD28 and CD27 and express Tim-3, PD-1 and CD40L. These cells do not produce IL-2, IFNg and TNF; a phenotype of senescent/exhausted T cells commonly increased in patients with different cancer and chronic infections. We hypothesize that after infiltrating the tumor mass, senescent T cells modulate other tumor-infiltrating cells like macrophages (Mo) and this may impact in the antitumoral response. To study this, autologous Mo were co-incubated with CD4+ or CD8+ TIST or controls (CD4+ or CD8+ T cells without tumor co-incubation). After LPS stimulation, we evaluated cytokines in supernatant. Mo cultured with CD4+ and CD8+ TIST showed higher production of pro-inflammatory cytokines (TNF, IL-1b and IL-6) and a lower production of IL-10 than Mo co-incubated with controls (p