FoxP3+Helios+, but not FoxP3+Helios-, Tregs express GARP and LAP, representing the expanded subpopulation in pancreatic cancer patients (TUM2P.911)

Abstract

Abstract Recent evidences show that Tregs negatively impact anti-tumour immunity and cancer immunotherapy. We, and others, reported that Tregs are expanded in peripheral blood and tumour microenvironment of cancer patients, correlating with poor prognosis and reduced survival. Our work has further established that Treg infiltration of tumors is correlated with a lack of patients’ responsiveness to therapy. Recent observations indicate that Tregs could be phenotypically and functionally different in cancer settings. However, molecules contributing to their enhanced immunosuppressive activity are yet to be elucidated. We recently found that the majority of peripheral and tumor-infiltrating FoxP3+ Tregs expresses Helios, an Ikaros family transcription factor. Interestingly, FoxP3+Helios+ Treg subset is significantly higher in cancer patients, compared to healthy individuals. Herein we show that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are mainly expressed on FoxP3+Helios+ Treg subset, but not on FoxP3+Helios- Treg subset. Additionally, FoxP3+Helios+GARP+LAP+ activated Tregs represent the expanded subset in pancreatic cancer patients, compared to controls. Taken together, these observations confirm that the expanded FoxP3+Helios+ Tregs in cancer patients represent the activated Treg subset, with more suppressive characteristics, that could be targeted by specific protocols.