Article Text

Download PDFPDF

873 Radiation-induced dynamic alterations in PD-1/PD-L1 activity and relevant immune cell profiles depending on treatment response status in mouse tumor models
  1. Yi Na Yoon1,
  2. Yu Jin Lim2 and
  3. Jae-Sung Kim1
  1. 1Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea
  2. 2Kyung Hee University College of Medicine, Seoul, Republic of Korea


Background In order to assess the immunologic effects of anti-cancer treatment and their therapeutic implications, we investigated the dynamic changes in programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) expression patterns caused by radiotherapy (RT).

Methods In the CT26 mouse model, local RT with 2 Gy × 5 or 7.5 Gy × 1 was treated on the tumors. Tumors were excised and analyzed at certain time points depending on radiation response status: baseline, early (immediately after RT), middle (beginning of tumor reduction), late (stable state with RT impact), and progression (tumor regrowth). The activity of PD-1/PD-L1 and associated immune cell profiles were quantitatively measured.

Results RT potentiated PD-L1 expression levels in tumor cells from the middle to the late phase, which thereafter dropped to the equivalent PD-L1 levels to baseline in the progression phase. The fractionated RT treatment resulted in a lower degree of tumor regression than the 7.5 Gy regimen, although the frequency of PD-L1+ myeloid-derived suppressor cells remained greater. In the progression phase, the frequency of PD-1+ and interferon (IFN)-γ+ CD8 T cells was increased, meanwhile the mean fluorescence intensity (MFI) values of IFN-γ started to drop. The proportion of PD-1+CD8+ T cells in the spleen was dramatically increased and maintained longer with 2 Gy × 5. Further, we confirmed that RT promoted the overall transcription levels of immune-related genes in the transcriptome data, supporting previously confirmed sequential patterns.

Conclusions According to time-course radiation responses, the dynamic changes in PD-1/PD-L1 activity were analyzed. The sequential patterns and dose-fractionation effects should be considered to determine relevant radioimmunotherapy regimens.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.