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.
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