biostudies-literatureGoods BANIAID NIH HHSNational Cancer InstituteNational Institutes of HealthGregory M. Kiez and Mehmet Kutman FoundationNIGMS NIH HHSe0181538https://www.ebi.ac.uk/biostudies/studies/S-EPMC5589094biostudies-literatureUnknown12(9)Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) have been highly successful in the treatment of cancer. While PD-1 expression has been widely investigated, its role in CD4+ effector T cells in the setting of health and cancer remains unclear, particularly in the setting of glioblastoma multiforme (GBM), the most aggressive and common form of brain cancer. We examined the functional and molecular features of PD-1+CD4+CD25-CD127+Foxp3-effector cells in healthy subjects and in patients with GBM. In healthy subjects, we found that PD-1+CD4+ effector cells are dysfunctional: they do not proliferate but can secrete large quantities of IFNγ. Strikingly, blocking antibodies against PD-1 did not rescue proliferation. RNA-sequencing revealed features of exhaustion in PDPloS oneFunctional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme.PMC5589094P30-CA14051P01 AI039671P01 AI073748T32 GM007205P01 AI045757Hernandez ALLucca LECoric VLove JCLowther DEHafler DALerner BAGunel MRaddassi KGoods BAfalseFunctional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme.Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) have been highly successful in the treatment of cancer. While PD-1 expression has been widely investigated, its role in CD4+ effector T cells in the setting of health and cancer remains unclear, particularly in the setting of glioblastoma multiforme (GBM), the most aggressive and common form of brain cancer. We examined the functional and molecular features of PD-1+CD4+CD25-CD127+Foxp3-effector cells in healthy subjects and in patients with GBM. In healthy subjects, we found that PD-1+CD4+ effector cells are dysfunctional: they do not proliferate but can secrete large quantities of IFNγ. Strikingly, blocking antibodies against PD-1 did not rescue proliferation. RNA-sequencing revealed features of exhaustion in PD2017-01-01T00:00:00Z20172026-05-03T01:15:25.81Z2019-03-27T02:55:43ZS-EPMC55890942888090310.1371/journal.pone.0181538