“Tumor induced senescence T-lymphocytes (TIST) modulate the activation of human monocytes”

RAMELLO MC; ACOSTA RODRIGUEZ EV; MONTES CL

Buenos Aires

Congreso; Primer Congreso Franco-Argentino de Inmunologia; 2010

Sociedad Argentina de Inmunologia - Sociedad Francesa de Inmunologia

We have previously 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 undergo tumor induced senescence. We and others have reported the suppressive effects of TIST cells on the adaptive immune system; our current aim is to investigate TIST cell effects on innate immune cells. To this end, autologous monocytes were coincubated with CD4+ or CD8+ TIST or control T cells (CD4+ or CD8+ T cells without tumor co-incubation) in the presence of anti-CD3 mAbs during 40 h, then macrophage classical or alternative activation markers were studied by flow cytometry. CD8+TIST cells induced a reduction in CD14 expression on monocytes compared to monocytes cocultured with controls (p<0,005). We also observed that the percentage of CD16+CD14+ was significantly increased in monocytes coincubated with CD4+ or CD8+ TIST in comparison to control T cells (CD4: TIST 28%±11 vs control 9%±2; CD8: TIST 28%±9 vs control 9%±4). In addition, a higher percentage of monocytes coincubated with CD4+ or CD8+ TIST were CD163+ (CD4: TIST 26%±5,6 vs control 13,5%±0,7; CD8: TIST 20%±1,4 vs control 6,5%±0,7) but expressed lower levels of CD206 (p<0,005 for CD4+TIST, p<0,001 for CD8+TIST) when compared to controls. The expression of HLA-DR molecules were upregulated in monocytes treated with CD4+TIST (p<0,002) while the expression of coestimulatory molecules such as CD86 and B7H4 were not affected by the presence of CD4+ or CD8+ TIST. We next assessed by flow cytometry the phagocytic ability as well as nitric oxide (NO) and reactive oxygen species (ROS) production of TIST-treated monocytes. We observed an increase in the percentage of phagocytosing monocytes following CD8+ TIST coculture and a reduction in the percentage of NO and ROS producer- monocytes after culture with CD4+ or CD8+ TIST. Taken together our results demonstrated that TIST cells are able to modulate monocytes/macrophages. We hypothesize that after infiltrating the tumor mass, monocyte/macrophage activity will be affected by not only the tumor microenvironment but also the presence of TIST and this may have important consequences for antitumoral immune response.