Tumor-induced senescent T cells promote the secretion of pro-inflammatory cytokines and angiogenic factors by human monocytes/macrophages through a mechanism that involves Tim-3 and CD40L

RAMELLO MC; TOSELLO BOARI J; CANALE FP; MENA HP; NEGROTTO S; GASTMAN B; GRUPPI A; ACOSTA RODRIGUEZ EV; MONTES CL

Cell Death & Disease

NATURE PUBLISHING GROUP

Año: 2014

2041-4889

olid tumors are infiltrated by immune cells where macrophages and senescent T cells are highly represented. Within the tumor microenvironment, a cross-talk between the infiltrating cells may occur conditioning the characteristic of the in situ immune response. Our previous work showed that tumors induce senescence of T cells which are powerful suppressors of lympho-proliferation. In this study, we report that Tumor-Induced Senescent (TIS)-T cells may also modulate monocyte activation. To gain insight into this interaction, CD4+ or CD8+ TIS-T or Control-T cells were co-incubated with autologous monocytes under inflammatory conditions. After co-culture with CD4+ or CD8+ TIS-T cells, monocytes/macrophages exhibit a high percentage of CD14+CD16+ cells and a reduced expression of CD206. These monocytes/macophages produce nitric oxide and reactive oxygen species; however, TIS-T cells do not modify phagocyte capacity of monocytes/macrophages. TIS-T modulated-monocytes/macrophages show a high