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

RAMELLO, MARIA CECILIA; CANALE, FERNANDO P.; BOSSIO, SABRINA N.; NUÑEZ, NICOLAS; DEL CASTILLO, ANDRÉS; LEDESMA, MARTA; PIAGGIO, ELIANE; GRUPPI, ADRIANA; ACOSTA RODRIGUEZ E V; MONTES, CAROLINA LUCIA

Mar del Plata

Congreso; LXIV Reunión científica anual de la Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE.; 2016

Sociedad Argentina de Inmunología, en conjunto con la reunión anual de SAIC y SAFE.

009 (939) SENESCENT T CELLS FROM BREAST CANCERPATIENTS ARE ARRESTED IN THE CELL CYCLE BUTSHOW POLYFUNCTIONAL EFFECTOR PHENOTYPEMaría Cecilia Ramello1, Fernando Pablo Canale1, SabrinaNoemí Bossio1, Nicolás Gonzalo Núñez2, Andrés Del Castillo3,Marta Ledesma3, Eliane Piaggio2; 4, Adriana Gruppi1,Eva Virginia Acosta Rodríguez1, Carolina Lucía Montes1.1Centro de Investigaciones en Bioquímica Clínica e Inmunología(CIBICI-CONICET), Departamento de BioquímicaClínica, Facultad de Ciencias Químicas, Universidad Nacionalde Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria,Córdoba, Argentina. 2Institut Curie, PSL ResearchUniversity, INSERM U932, F-75005, Paris, France. 3HospitalRawson, Av. Gdor Amadeo Sabattini 2025, Polo Sanitario,Córdoba, Argentina. 4Centre d?Investigation Clinique BiothérapieCICBT 1428, Institut Curie, Paris, F-75005 France.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 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 patientsand 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-producerscompared to donors (p=0.008). Moreover, there was a similartrend, although not statistically significant, 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.