SENESCENT T CELLS FROM BREAST CANCER PATIENTS ARE ARRESTED IN THE CELL CYCLE BUT SHOW POLYFUNCTIONAL EFFECTOR PHENOTYPE

RAMELLO M CECILIA; CANALE F; BOSSIO S; NUÑEZ NICOLAS; DEL CASTILLO A; LEDESMA M; PIAGGIO E; GRUPPI A; ACOSTA RODRIGUEZ EV; MONTES CL

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología. Mar del Plata. Noviembre 2016.; 2016

SAI

Tumor-induced dysfunction of T cells in patients with cancermay contribute to immune escape. Exhaustion and senescenceof T cells have been described as dysfunctional states inducedin cancer patients. KLRG-1 and CD57 have been considered assenescent markers in aged T cells. Herein, we aim to study thephenotypic and functional characteristics of senescent T cellsfrom breast cancer patients. We observed that the frequencyof KLRG-1+CD57+ T cells (CD8+ and CD4+) were significantlyincreased in peripheral blood of cancer patients compared tohealthy donors (p=0.019 and 0.025, respectively). We confirmedthat KLRG-1+CD57+ T cells showed a senescent phenotype sincethey were CD27-CD28-, gH2AX+ and exhibited the highest activityof b-galactosidase. CD57+ T cells (CD8+ and CD4+) exhibitedhigher frequency of cell-cycle arrested cells than CD57- T cells(p=0.005 and 0.001, respectively). Interestingly, these populationsexhibited co-expression of inhibitory receptors such as 2B4,BTLA and CD160 but not PD-1. Moreover, we found that KLRG1+CD57+CD8+T cells and KLRG-1+CD57- or KLRG-1-CD57+CD4+ T cells infiltrate tumors and metastatic-draining lymphnodes from breast cancer patients. Senescent T cells exhibitedhigher ability to produce IFNg and TNF and increased capacityto degranulate compared to non-senescent T cells in all tissuesstudied (p