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

ABRATE C; BOSSIO S; BOCCARDO S; RODRIGUEZ C; GRUPPI A; ACOSTA RODRIGUEZ E; MONTES C

Buenos Aires

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

SAIC. SAI. SAFIS.

Previously we have demonstrated that tumor-infiltrating exhaustedCD8+ T cells exhibit high expression of CD39. CD39 is an ecto-enzymethat participates in the generation of adenosine, an immunosuppressivemolecule that interferes with many anti-tumor immuneresponses. In this work, we aimed to evaluate the impact of CD39expression on tumor progression and in the cellular compositionwithin tumor microenvironment. For this, C57BL/6 wild type (WT)and CD39 KO mice were injected with B16F10-OVA tumor cells.We evaluated tumor progression by measuring tumor volume atdifferent days post-injection (dpi, 7, 10, 12, 14 and 17). Additionallyon day 17 we evaluated different tumor?infiltrating immune cellpopulations by flow cytometry. We observed no significant differenceson tumor volume at any dpi evaluated in both groups. Whilesimilar frequencies of tumor-infiltrating (TI) B cells, CD4+ T cells,macrophages, NK, Dendritic cells was observed in CD39KO andWT tumor-bearing mice, CD39 KO mice exhibit higher frequencyof TI-CD8+ T cells (p<0.0001) and higher % of TI-CD8+ T cells witheffector phenotype (CD44+CD62L-) (p<0.05). Accordingly, CD39KO tumor-bearing mice show higher frequency of OVA-specific TICD8+T cells than WT mice (p<0.01). We also evaluate the expressionof inhibitor receptors (iR) (PD-1, LAG-3 and TIM-3) as well astranscription factors (TF) (EOMES, TBET, IRF-4 and TOX) relatedto exhaustion. We found no statistic differences in the frequency ofTI-CD8+ T cells co-expressing 3 IR and FT from CD39KO and WTmice. Together our results suggest that the absence of CD39 mayfavor the recruitment of CD8+ T cells with effector phenotype intothe tumor microenvironment, reinforcing the idea that CD39 couldbe consider as a promising target in the anti-tumor immunotherapy.CD39, CD8+ T Lymphocyte, Tumor, Exhaustion