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Int J Radiat Biol. 2018 May;94(5):488-494. doi: 10.1080/09553002.2017.1400192. Epub 2017 Nov 29.

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

Author information

1
a Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin , China.
2
b Department of Biochemistry and Molecular & Cellular Biology , Georgetown University , Washington , DC , USA.
3
c Department of Oncology , Georgetown University , Washington , DC , USA.

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); T cells; checkpoint blockade; ionizing radiation

PMID:
29108460
DOI:
10.1080/09553002.2017.1400192
[Indexed for MEDLINE]

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