4PD1^hi T cells

Cancer Cell 33, 1017–1032 (2018)

Cancer clinical trials are underway to target the immunological co-inhibitory receptors PD-1 or CTLA-4; however, such checkpoint therapies are effective in only a fraction of patients. In Cancer Cell, Zappasodi et al. identify a population of suppressor CD4⁺Foxp3^– T cells, called ‘4PD1^hi T cells’, that accumulate within tumors and are poor prognostic indicators. 4PD1^hi T cells are able to inhibit both CD4⁺ effector cells and CD8⁺ effector cells. RNA-based sequencing expression profiles show that 4PD1^hi T cells are distinct from Foxp3⁺ regulatory T cells; instead, these cells resemble CD4⁺ follicular helper T cells. In melanoma models and in patients, mono-therapy with antibody to PD-1 diminishes the frequency of 4PD1^hi T cells, whereas antibody to CTLA-4 increases their frequency, which suggests that clinical monitoring of 4PD1^hi T cells is warranted for treatment decisions.