KLRG-1+CD57+ CD4+ senescent T cells are increased in peripheral blood from breast cancer patients and display differential genes expression compared to CD4+ senescent t cells from healthy donors

CANALE, FERNANDO P.; RAMELLO, MARÍA C.; NÚÑEZ, NICOLÁS; MUÑOZ, MARCOS; BOSSIO, SABRINA N.; ABRATE, CAROLINA; PIAGGIO, ELIANE; GRUPPI, ADRIANA; RODRÍGUEZ, EVA V. ACOSTA; MONTES, CAROLINA L.

Congreso; Reunión Conjunta de las Sociedades de Biociencias. LXV Reunión Anual de la SAI 2017; 2017

Cell senescence is a phenotype characterized by cell cycle arrest,usually due to DNA damage, and alterations in cells functionality.Senescence in CD8+ T cells has been widely described, while senescent CD4+ T cells have been less studied, particularly in cancerpatients. In this work we explored the phenotype of CD4+ T cellsin peripheral blood of breast cancer patients (BCPs). Using FACSwe identifed senescent T cells using the classic markers KLRG-1and CD57. KLRG-1+CD57+CD4+ T cells (DP cells) were increasedin BCPs compared to age-matched healthy donors (HDs; p≤0.05).Comparing with KLRG-1-CD57-CD4+T cells (DN) from BCPs, theseDP cells showed lower expression of CD28 and CD27 (p≤0.05), cellcycle arrest and lower IL-2 production (p≤0.01), all features of senescent T cells. To identify biological functions and pathways associatedwith CD4+ T cell senescence, we sorted DN and DP cells from 4BCPs and also DP cells from 3 HDs and performed a transcriptomestudy by Microarrays (Affymetrix). We found 1115 differential-expressed genes (DEGs) between DP cells from BCPs and HDs and1170 between DN and DP cells from BCPs (Welch t-test applied,p≤0.05 for all DEGs). Gene Ontology analysis (DAVID databases)comparing DP cells from BCPs and HDs showed upregulation inthe former of genes related to DNA repair and protein glycosylationand downregulation of genes related to apoptosis, proliferation andRNA splicing. Comparing DP cells vs. DN cells from BCPs, manyDEGs were related to immune response. Among them, genes related to TCR signaling and co-stimulation were downregulated inDP cells. Our results show that even though DP cells from HDs andBCPs were sorted using same markers, the transcriptome studyrevealed differences, particularly in genes related to biological processes as DNA repair, proliferation and survival. Further studies willbe conducted to identify markers of cancer-promoted senescenceon CD4+ T cells and the role of these cells in tumor progression.