Peripheral Circulating CD45RA-FOXP3hi T Regulatory (TReg) II Cells Provide a Window into the Activity of Intratumoral TReg Cells.

The immune landscape of cancer determines its responsiveness to immunotherapy. Tumors infiltrated with CD8+ T cells (immune-active tumors) are more likely to respond to immunomodulatory agents. However, immune activation often is counterbalanced by strong immunosuppressive mechanisms that are necessary to maintain homeostasis but consequentially can facilitate the survival of cancer cells in the immunocompetent host, a concept defined as compensatory immune suppression. TReg cells contribute to compensatory immune suppression, and therapies targeting the immunosuppressive TReg population are being actively explored. Wang et al. characterize a subset of peripheral circulating CD45-FOXP3hi TReg II cells that phenotypically and functionally parallel the activity of their intratumoral counterparts. The findings are paradigm shifting and may provide a potential liquid-based tool to evaluate the immunosuppressive activity of intratumoral TReg cells; they may also allow temporal assessment of whether the fine balance between immune rejection versus tolerance is achieved with various applied therapies.