TUMOR-INFILTRATING CD39+ CD4+ FOXP3NEG CELLS: AN UNKNOWN POPULATION WITH FEATURES OF EXHAUSTION

ABRATE C; ACOSTA RODRIGUEZ EV; RODRIGUEZ C; MONTES CL; BOSSIO S; GRUPPI A

Tucuman

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

TUMOR-INFILTRATING CD39+ CD4+ FOXP3NEG CELLS: AN UNKNOWN POPULATION WITH FEATURES OF EXHAUSTIONSabrina N. Bossio1, Carolina Abrate1, Constanza G. Rodriguez1, Eliane Piaggio2,3, Adriana Gruppi1, Eva V. Acosta Rodriguez1, Carolina Montes1.1Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.2Institut Curie, PSL Research University, INSERM U932, F-75005, Paris, France.3Centre d?Investigation Clinique Biothérapie CICBT 1428, Institut Curie, Paris, F-75005 France.The role of the CD4+T cells in the immune response against cancer is poorly understood. Previously we demonstrated that tumors from tumor bearing-mice showed an important infiltrate of FOXP3neg CD4+ cells (Tconv) expressing CD39. CD39 is an ecto-enzyme capable to hydrolyze extracellular ATP within the tumor microenvironment. We aim to determine if this CD39+Tconv population exhibit a phenotype associated to exhaustion. C57BL/6 mice were injected with B16F10-OVA cancer cells and tumors were extracted on day 17. We detected that CD39+Tconv exhibit an increased expression of PD-1, Lag-3, TIGIT and CTLA-4 compared to the expression on CD39-Tconv cells (p≤0.05 for all). Within CD39+Tconv cells, 78% expressed inhibitory Receptors (iRs). Around 30% of this population expressed one, 34% co-expressed 2 while 14% co-expressed 3 iRs. Despite of 30% of CD39-Tconv expressed iRs, most of them expressed only one. The analysis of transcription factors showed an increased expression of T-bet, Eomes, Helios, c-Maf and Blimp-1 in CD39+Tconv compared to CD39-Tconv (p≤0.05 for all). CD39+Tconv depicted a higher frequency of Ki67+ cells than their counterpart (p≤0.01). Adoptive transfer of OTII CD39-cells to B16-OVA injected WT mice demonstrated that 98,08±1,73% of OTII cells in lymph nodes expressed CD39, indicating that tumor antigen specific T cells acquired the ecto-enzyme expression. The study of breast cancer patients unveiled an expansion of CD39+Tconv in tumors that was more evident comparing to juxtatumor (p≤0.01). Altogether these results indicate that CD39+Tconv cells represent an heterogeneous population within tumor microenvironment with features of exhaustion. Further studies will confirm the hypothesis.Keywords: CD4, cancer, CD39, tumor, inhibitory receptors.