Programmed cell death-1 receptor deficiency enhances CD30+ T regulatory cell function in Melanoma [Murine scRNAseq]
Regulatory T cells (Tregs) are vital for immune suppression rendering their function through multiple pathways including the expression of co-inhibitory receptors. The role of co-receptors namely PD1 in Treg function remains controversial. We demonstrate that PD1 is a master checkpoint in Tregs controlling several aspects of Treg biology in tumor immunity. Our data demonstrates that PD1 controls the expression and function of a unique co-inhibitory receptor network that dictates Treg function. We found that CD30 plays a central role within this network in driving Treg suppressive function within the tumor microenvironment (TME). Mechanistically, PD1 deficiency unleashed enhanced STAT5 signaling in Tregs, which drove CD30 expression. Our work highlights a new role for PD1 as a checkpoint that negatively controls CD30 expression in Tregs thereby dampening their function. Understanding the landscape changes that PD1 renders to Treg function can enable the use of combination therapies for better treatment outcomes in cancer. Overall design: Tumors were harvested from C57BL/6 WT and B6.PD1KO mice. Tumour infiltrating lymphocytes were isolated from B16 tumor using ficol density gradient centrifugation. Cells were then debulked with Thy1 microbeads and then stained with sample tags and Abseq antibodies along with Lineage cocktail antibodies and Thy1. Lin+Thy1+ cells were enriched through flow sorting and then loaded onto cartridge and subjected to Rhapsody analysis.