Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells Deguan Li Renxiang Chen Yi-Wen Wang Albert J. Fornace Jr. Heng-Hong Li 10.6084/m9.figshare.5576518.v2 https://tandf.figshare.com/articles/journal_contribution/Prior_Irradiation_Results_in_Elevated_Programmed_Cell_Death_Protein_1_PD-1_in_T_Cells/5576518 <p><b>Purpose:</b> In this study we addressed the question whether radiation-induced adverse effects on T cell activation are associated with alterations of T cell checkpoint receptors.</p> <p><b>Materials and methods:</b> Expression levels of checkpoint receptors on T cell subpopulations were analyzed at multiple post-radiation time points ranging from one to four weeks in mice receiving a single fraction of 1 or 4 Gy of γ-ray. T cell activation associated metabolic changes were assessed.</p> <p><b>Results:</b> Our results showed that prior irradiation resulted in significant elevated expression of programmed cell death protein 1 (PD-1) in both CD4+ and CD8+ populations, at all three post-radiation time points. T cells with elevated PD-1 mostly were either central memory or naïve cells. In addition, the feedback induction of PD-1 expression in activated T cells declined after radiation.</p> <p><b>Conclusion:</b> Taken together, the elevated PD-1 level observed at weeks after radiation exposure is connected to T cell dysfunction. Recent preclinical and clinical studies have showed that a combination of radiotherapy and T cell checkpoint blockade immunotherapy including targeting the programmed death-ligand 1 (PD-L1)/PD-1 axis may potentiate the antitumor response. Understanding the dynamic changes in PD-1 levels in T cells after radiation should help in the development of a more effective therapeutic strategy.</p> 2017-11-29 17:43:05 Programmed cell death protein 1 (PD-1) ionizing radiation T cells checkpoint blockade