The depths of PD-1 function within the tumor microenvironment beyond CD8+ T cells

Programmed cell death-1 (PD-1; CD279) is a cell surface receptor that is expressed in both innate and adaptive immune cells. The role of PD-1 in adaptive immune cells, specifically in CD8+ T cells, has been thoroughly investigated but its significance in other immune cells is yet to be well established. This review will address the role of PD-1 based therapies in enhancing non-CD8+ T cell immune responses within cancer. Specifically, the expression and function of PD-1 in non-CD8+ immune cell compartments such as CD4+ T helper cell subsets, myeloid cells and innate lymphoid cells (ILCs) will be discussed. By understanding the immune cell specific function of PD-1 within tissue resident innate and adaptive immune cells, it will be possible to stratify patients for PD-1 based therapies for both immunogeneic and non-immunogeneic neoplastic disorders. With this knowledge from fundamental and translational studies, PD-1 based therapies can be utilized to enhance T cell independent immune responses in cancers.