ESTRO 2025 - Abstract Book

S3882

Radiobiology - Immuno-radiobiology

ESTRO 2025

3301

Digital Poster Impacts of combining pulsed low dose rate radiotherapy and anti-PD-1 antibody on tumor growth and its mechanism for lung cancer in mice. Rui Huang 1 , Shouyan Yin 1,2 , Jinyi Lang 1 , Peng Zhang 1 1 Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation oncology Key Laboratory of Sichuan Province, Chengdu, China. 2 Graduate School, Chengdu Medical College, Chengdu, China Purpose/Objective: This study investigated the inhibitory effect of PLDR combined with anti-PD-1 antibody on lung cancer in mice and its impact on tumor immune microenvironment. Material/Methods: By transplanting murine LLC cells into the right leg of C57BL/6 mice with immune activity, a transplanted subcutaneous tumor model was established.The mice were randomly divided into five groups:control 、 conventional radiotherapy(RT)±anti-PD-1 antibody (mAb) 、 PLDR±anti-PD-1 antibody (mAb).RT was delivered as a dose of 5 × 2 Gy whereas PLDR involved delivering a dose of 2 Gy as 10 pulses of 0.2 Gy, each 3 minutes apart and lasting for 5 days.Anti-PD-1 antibody and isotype control were administered intraperitoneally once every three days at a dose of 5mg/kg,three times in total.The tumor 、 blood and tumor-draining lymph nodes (TDLNs) were harvested after treatment, and a single cell suspension was prepared for flow cytometry to analyze the changes in the immune microenvironment of the tumor tissue 、 the expression of PD-L1 、 PD-1 and the activated systemic immune response. both RT and PLDR induced up-regulation of PD-L1 expression on tumor surface and PD-1 expression on lymphocytes.Then, the frequency of CD4+ 、 CD8+T cells were higher in the PLDR combined treatment group in tumor blood and draining lymph nodes, and synergistically reduce the local accumulation of tumor-infiltrating myeloid-derived suppressor cells(MDSCs) than others.Furthermore,the main reason for the better tumor inhibition effect of PLDR combined group is that it upgrades the number and activity of CD8+T cells in tumor.Finally,we found the efficacy of PLDR combined with PD-1 blockade was associated with reduced CD11b+Gr1+ myeloid cell infiltration and enhanced CD45+CD8+T cell infiltration with concomitant up-regulation of T-cell activation,activate the activity of DCs cells at 7 days post-combined treatment.In the PLDR combination group,we observed the proportion of MDSCs rapidly increased to the same level of the control group after depletion of CD8+T cells,and observed more significants increasing when compared with RT combination group. Conclusion: The up-regulated of PD-L1 depended on CD8+T cells in the tumor microenvironment when mice underwent PLDR.PLDR combined with anti-PD-1 can increase infiltration of CD8+T cells into the tumor tissue, effectively stimulate the maturation and activation of DCs in lymph nodes,reduce the accumulation of MDSCs,thereby changing the tumor microenvironment and achieving the synergistic effect of inhibiting the growth of mouse lung cancer, which extending the survival period. Results: Survival analysis demonstrated a statistically significant advantage for PLDR+anti-PD-1 than other group.Meanwhile

Keywords: PLDR,anti-PD-1 antibody

References: [1]Meric-Bernstam F, Larkin J, Tabernero J, et al. Enhancing anti-tumour efficacy with immunotherapy combinations[J]. The Lancet, 2021, 397(10278): 1010–1022. [2] Huang, R, Li, Z, Yang, F, et al. Efficacy and safety of PLDR-IMRT for the re-irradiation of recurrent NPC: A prospective, single-arm, multicenter trial. Cancer Sci. 2023; 114: 2534- 2543. doi:10.1111/cas.15759