CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Signals through TCR stimulation trigger CD39 expression on CD8+ T cells from lymph node from B16F10-OVA tumor-bearing mice.
Autor/es:
ACOSTA RODRÍGUEZ, EVA; CANALE, FERNANDO P.; MONTES, CAROLINA L.; BOSSIO, SABRINA N.; GRUPPI, ADRIANA; ABRATE, CAROLINA P.
Lugar:
Buenos Aires
Reunión:
Congreso; LXV Reunión Anual de la Sociedad Argentina de Inmunología; 2017
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
CD39 and CD73 play strategic roles in tumor microenvironment.We demonstrated that exhausted CD8+ T cells with high expressionof CD39 infiltrate tumors, however, they are absent in lymphoid organs.We aimed to evaluate signals that may influence CD39 up-regulationon CD8+ T cells. Purified CD8+ T cells from draining lymphnode of B16 OVA-tumor bearing mice were stimulated with tumorcells culture supernatant or anti-CD3/CD28 in the presence of IL-6or IL-27 (cytokines that promote exhaustion). Tumor supernatants orTCR stimulation alone for 72hs did not modify CD39 expression observedex vivo, however, IL-27 drove CD39 expression on anti-CD3/antiCD28 stimulated cells (p≤0,05) especially when combined withIL-6 (p≤0,0001) compared to anti-CD3/antiCD28 alone. CD39+ cellsdid not express CD73, but they showed increment of PD-1 (p≤0, 05)and slight increase of Tim-3 upon culture with IL-27. In this samecondition, stimulated CD8+ CD39+ T cells showed lower frequencyof IFNg+ and TNF+ cells than CD8+ T cells stimulated throughTCR (p≤0,05 and p≤0,01). Longer stimulation with anti-CD3/CD28(48hs, resting 4 days in IL-2 and 24hs of re-stimulation) triggeredhigh CD39, PD-1 and Tim-3 expression on CD8+ T cells respect tounstimulated controls. Stimulation of PBMCs from breast cancerpatients through TCR (72hs) induced CD39 expression on CD8+ Tcells (p≤0,05) compared to non-stimulated cells, however purifiedhuman CD8+ T cells stimulated with anti-CD3/anti-CD28 exhibitedlower percentage of CD39+ cells compared to CD8+ T cells from totalPBMCs (8,5%vs52,3%), but this percentage increased in the presenceof IL-27 or the combination of IL-6 and IL-27 (17% and 24%respectively). After TCR stimulation in presence of IL-27 plus IL-6,human CD8+CD39+ T cells exhibited higher expression of PD-1 thanCD8+ T cells stimulated with anti-CD3/anti-CD28 alone. Altogetherthese results demonstrated that signal through TCR and cytokinesinvolved in exhaustion trigger CD39 upregulation.