ABSENCE OF CD39 FAVORS INFILTRATION OF TUMORS WITH CD8+ T LYMPHOCYTES WITH EFFECTOR PHENOTYPE

ABRATE, CAROLINA; BOSSIO, S.N.; BOCCARDO, SANTIAGO; CONSTANZA RODRIGUEZ; GRUPPI, ADRIANA; RODRÍGUEZ, EVA V. ACOSTA; MONTES, CAROLINA L.

Congreso; Reunión Anual de Sociedades de Biociencias. SAIC - SAI - SAFIS; 2020

Previously we have demonstrated that tumor-infiltrating exhausted CD8+ T cells exhibit high expression of CD39. CD39 is an ecto-enzyme that participates in the generation of adenosine, an immunosuppressive molecule that interferes with many anti-tumor immune responses. In this work, we aimed to evaluate the impact of CD39 expression on tumor progression and in the cellular composition within tumor microenvironment. For this, C57BL/6 wild type (WT) and CD39 KOmice were injected with B16F10-OVA tumor cells. We evaluated tumor progression by measuring tumor volume at different days post-injection (dpi, 7, 10, 12, 14 and 17). Additionally on day 17 we evaluated different tumor?infiltrating immune cell populations by flow cytometry. We observed no significant differences on tumor volume at any dpi evaluated in both groups. While similarfrequencies of tumor-infiltrating (TI) B cells, CD4+ T cells, macrophages, NK, Dendritic cells was observed in CD39KO and WT tumor-bearing mice, CD39 KO mice exhibit higher frequency of TI-CD8+ T cells (p<0.0001) and higher % of TICD8+ T cells with effector phenotype (CD44+CD62L-) (p<0.05). Accordingly, CD39 KO tumor-bearing mice show higher frequency of OVA-specific TI-CD8+T cells than WT mice (p<0.01). We also evaluate the expression of inhibitor receptors (iR) (PD-1, LAG-3 and TIM-3) as well as transcription factors (TF) (EOMES, TBET, IRF-4 and TOX) related to exhaustion. We found no statistic differences in the frequency of TI-CD8+ T cells co-expressing 3 IR and FT from CD39KO and WT mice. Together our results suggest that the absence of CD39may favor the recruitment of CD8+ T cells with effector phenotype into the tumor microenvironment, reinforcing the idea that CD39 could be consider as a promising target in the anti-tumor immunotherapy.