Study of Foxp3 expression in tumor microenvironment and peripheral blood of breast cancer patients

Romina Canzoneri¹, Ezequiel Lacunza¹, Carolina Berman¹, Paulina Melchiori¹, Betiana Ermili¹, Aldo Creton², Luis A Barbera², Maria Virginia Croce¹, Marina Teresita Isla Larrain¹

Several clinical trials combining immune checkpoints inhibitors are in course both in breast cancer (BC) and in other tumors. In this sense, the study of the role of immune regulation in cancer is relevant. Foxp3 is known as a Treg marker, but also has been detected in tumor cells, being a controversial finding. The aim of this study was to evaluate Foxp3 expression in the tumor microenvironment and in peripheral blood mononuclear cells (PBMC) from BC patients. Tumor and peripheral blood from 127 breast cancer patients without treatment were obtained during surgery with informed consent. Foxp3 and other variables (ER, PR, HER2, CD8, TILs) were analyzed by IHC in tumors and by PCR in PBMC, and statistical analysis was performed considering also histopathological variables. In silico analysis of FOXP3 and coexpressed genes was performed through RNAseq and microarrays databases. Foxp3 was found in 61% of BC samples, showing a positive correlation with CD8+ cells and a negative association with tumor stage. In 73.5% PBMC samples, FOXP3 expression was found showing a positive association with advanced tumor stages and PR (p<0.05). In silico analysis showed that FOXP3 and coexpressed genes are associated to immune pathways and FOXP3 RNA levels were higher in Basal and Her2 subtypes. The presence of Foxp3 in breast cancer cells and FOXP3 expression in PBMC associated with advanced stages, makes this transcription factor a potential target for immunotherapy.