Study of the modulatory role of different tumor-infiltrating CD8 T cells subpopulations

CANALE F; RAMELLO MC; ARAUJO FURLLÁN C; GOROSITO M; TOSELLO BOARI J; ADRIANA GRUPPI; ACOSTA RODRIGUEZ EV; MONTES CL

Buenos Aires

Congreso; I meeting LASID, FAIC and SAI; 2015

LASID, FAIC y SAI

BACKGROUND: CD8 T cells are crucial in tumor elimination. Nevertheless, exhausted and regulatory CD8 T cells have been described in cancer. We aimed to study the modulatory role of different subpopulations of tumor-infiltrating CD8 T cells. METHODS: C57BL/6 mice were injected with MO5 cells and tumors extracted 17-19 days later. Within tumor-infiltrating CD8 T cells we analyzed, by flow cytometry, three subpopulations according to inhibitory receptors´ expression: PD-1-Tim-3- (DN), PD-1+Tim-3- (SP) and PD-1+Tim-3+ (Tex: exhausted T cells). RESULTS: We observed higher % of SP and Tex cells with effector memory phenotype (CD44+CD62L-, 90% and 95% respectively), compared to DN cells (71%, p≤0.05). Analysis of modulatory molecules showed higher expression of PD-L1, PD-L2, FasL and CD39 on SP and Tex cells compared to DN cells (p≤0.05 for all). CD73, a molecule involved in generating suppressive adenosine was expressed by DN but not by Tex cells. To address a possible modulatory role of these populations we co-cultured stimulated CD4 T cells with DN, SP and Tex cells. CD4 T cells co-cultured with CD8 T cells do not exhibit differences in CD25 and CD69 expression, however CD4 T cells cultured with Tex and SP cells showed lower IFNg production compared with those cultured with DN cells (p≤0.05). CONCLUSIONS: CD8 T cell subpopulations exhibit differential expression of modulatory molecules, which may affect cytokine production by CD4 T cells. Studies will be conducted to understand the interaction of Tex and SP T cells with other cells in the tumor-microenvironment and the impact in tumor progression.