Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords:

• Programmed cell death protein 1 (PD-1)
• ionizing radiation
• T cells
• checkpoint blockade

Disclosure statement

The authors declare no competing financial interests.

Notes on contributors

Deguan Li received his PhD in 2012. He is currently an Assistant Professor at Institute of Radiation Medicine, Chinese Academy of Medical Sciences (CAMS).

Renxiang Chen received her PhD in 2004. She is a Research Associate at Georgetown University.

Yi-Wen Wang was a Research Assistant in Heng-Hong Li's laboratory.

Albert J. Fornace, Jr. is a highly-cited expert in stress signaling, molecular oncology, and radiobiology.

Heng-Hong Li is an Assistant Professor at Georgetown University. Her research focuses on investigation of transient and long lasting impacts of radiation on functions of immune cells.

Additional information

Funding

This work was supported by a research grant from National Natural Science Foundation of China [81372927], CAMS Innovation Fund for Medical Sciences [CIFMS, 2017-I2M-3-019], and a research grant from U.S. Department of Energy [DE-SC0002345].