CD39 expression on CD8+ tumor-infiltrating T cells is associated to effector memory phenotype and metabolic stress.

CONDAT F; ABRATE C; MONTES CL; BOSSIO SN; CANALE FP; ACOSTA RODRIGUEZ EV; GRUPPI A

Congreso; SAIC-SAI-SAFIS 2018.; 2018

Previously we have demonstrated that exhausted tumor-infiltratingCD8+ T cells (TILs) exhibit high expression of the ecto-nucleotidaseCD39. In this work we aimed to characterize the phenotypeof the CD39+ TILs. Using the B16-F10-OVA cancer model we determinedby FACS that CD8+CD39high TILS exhibited an effectormemory phenotype (CD62L-CD44+), while CD8+CD39-TIls representa heterogeneous population (central memory, effector memoryand naïve). CD8+CD39high TILS showed higher frequency ofKLRG-1+CD127- cells (short-live effector phenotype) than CD39lowCD8+TILS (p≤0,05). In addition, we observed that CD8+CD39highTILs showed higher expression of CD8α than CD39- or CD39int CD-8TILs (p≤0,0001 in both cases). In spleen and lymph node, CD39intCD8+T cells showed higher CD8α expression than CD39- cells.Similar results were observed in other cancer models like 4T1, MCAOVAand CT26. We also evaluated markers of metabolic stress andwe detected that CD8+CD39high TILS (obtained ex vivo) exhibitedhigher expression of p-mTOR, pS6 and p-AMPK than CD8+CD39-TILS (p≤0,005, p≤0,0001 and p≤0,001 respectively). After αCD3/αCD28 stimulation CD8+CD39highTILs showed lower expressionof pmTOR and PS6 than CD8+CD39-TILs (p≤0,05). Studying breastcancer patients we observed that high frequency of CD8+CD39+ Tcells from tumor or metastatic lymph node (MLN) showed a memoryeffector phenotype. Most of CD8+CD39- TILs cells exhibited phenotypeof central memory or effector memory while in MLN most ofthis population correspond to naïve phenotype. CD8+CD39+ TILsshowed higher expression of CD8α than CD39- TILs (p≤0,05). Alltogether or results demonstrated that expression of CD39 on CD8+T cells is associated to a short-live effector phenotype and metabolicstress. CD39 emerges as a target for treatments aimed to restoreCD8 T cells anti-tumor immunity.