Senescent T cells from breast cancer patients are arrested in the cell cycle but show polyfunctional effector phenotype

RAMELLO, MARÍA C.; CANALE, FERNANDO P.; BOSSIO, SABRINA N.; NÚÑEZ, NICOLÁS; DEL CASTILLO, ANDRÉS; LEDESMA, MARTA; PIAGGIO, ELIANE; GRUPPI, ADRIANA; RODRÍGUEZ, EVA V. ACOSTA; MONTES, CAROLINA L.

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) 2016; 2016

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 signifcantlyincreased in peripheral blood of cancer patients compared tohealthy donors (p=0.019 and 0.025, respectively). We confrmedthat 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 populations exhibited co-expression of inhibitory receptors such as 2B4,BTLA and CD160 but not PD-1. Moreover, we found that KLRG-1+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<0.05). KLRG-1+CD57+ peripheral CD4+ and CD8+ Tcells expressed higher levels of granzyme B and perforin thannon-senescent T cells (p<0.05). Senescent T cells from cancer patients and aged-matched healthy donors exhibited a polyfunctionaleffector phenotype, however we found that in peripheral blood ofpatients, KLRG-1+CD57+CD8+ T cells were higher TGFb-producers compared to donors (p=0.008). Moreover, there was a similartrend, although not statistically signifcant, in KLRG-1+CD57+CD4+T cells. Thus, our data suggest that senescent CD8+ and CD4+T cells are not completely dysfunctional cells in cancer patients.