ESTRO 2022 - Abstract Book

S1624

Abstract book

ESTRO 2022

Results The PD-L1 expressions on CD45 - cells markedly increased early on day 2 ‒ 7, but the alteration was subsequently attenuated and disappeared with tumor regrowth. The proportion of PD-1 + CD8 + T cells also increased, which was persistently maintained even after day 21. The initiation time points of the RT-induced changes differed according to dose regimens; an abrupt increase with single 7.5 Gy over day 2 ‒ 7, but delayed increase with 2 Gy x 5 over day 14 ‒ 21. The level of PD-L1 + myeloid-derived suppressor cells was elevated since day 2, and the increment was higher with single 7.5 Gy compared to 2 Gy x 5. PD-L1 expressions on M1/M2 tumor-associated macrophages and dendritic cells increased since day 7. Although local RT was insufficient to induce significant alterations in splenic CD8 + effector and Foxp3 + T cell levels, the amount of PD- 1 + CD8 + T cell subsets in spleen increased after RT. In the transcriptome analyses of tumor tissues, radiation-induced changes in cytokine activity, cytokine and chemokine-mediated pathway, and innate immune response were maximally observed at day 7; however, the changes were gradually attenuated over day 14 ‒ 21. Conclusion Local RT induced dynamic changes of tumor immune status relevant to PD-1/PD-L1 axis not only in T-cell immunity but also in myeloid-lineage immune cells. The altered profiles varied according to different phases of tumor regression and dose- fractionation regimens. The dynamicity of the radiation effect in the immunologic tumor microenvironment needs to be considered combining checkpoint blockade with RT. 1 Fondazione IRCCS Istituto neurologico Carlo Besta, Neurosurgery, Radiotherapy Unit, Milan, Italy; 2 University of Milan- Bicocca, Neuroscience, Milan, Italy; 3 Fondazione IRCCS Istituto neurologico Carlo Besta, Unit of Immunotherapy of Brain Tumors, Unit of Molecular Neuro-Oncology, Milan, Italy; 4 Fondazione IRCCS Istituto neurologico Carlo Besta, Health Department, Milan, Italy; 5 Fondazione IRCCS Istituto neurologico Carlo Besta, Radiotherapy Unit, Neurosurgery Department, Milan, Italy Purpose or Objective Radiotherapy (RT), providing immunomodulation on tumor microenvironment, can increase the sensitivity to the specific immune response of cold tumors such as glioblastoma (GBM). To investigate the RT effects as both exclusive and combinatorial strategies with immunotherapy (IT), we treated immune-competent glioma-bearing mice with both local fractionated RT and RT followed by dendritic cell (DC) IT. Materials and Methods GL261-glioma bearing mice were locally irradiated with a total dose of 15 Gy in 3 consecutive fractions of 5 Gy on day 7, 8, and 9 after tumor implantation. For combinatorial treatment, DC-IT were injected subcutaneously on day 16, 23, and 30 after tumor implantation. Changes in tumor microenvironment were investigated by assessing microglial and chemokine gene expression on gliomas of RT, RT-IT treated and control mice. The microglia cells from explanted tumours were analyzed as well. Results RT promoted a polarization from M2 to M1 of microglia/macrophages (GAMs) within the microenvironment, characterized by increased production of pro-inflammatory antitumor cytokines such as TNF- α and IFN- γ and high level of iNOS. Indeed, M2 phenotype markers, TGF- β 1 and IL-10, were significantly decreased in irradiated mice at the earlier time point (day 16). Moreover, RT-IT influenced CD45dim/CD11b+/CD172A+ microglia activation, characterized by a M1 signature, and CD4+ T cells recruitment as well as a robust infiltration of CD8+ T cells. The overall survival of glioma-bearing mice was higher in the RT-IT group. Conclusion Our preliminary data suggest that the RT-IT combination is efficient in promoting a proinflammatory microenvironment and re-educating microglia as anti-tumor effector cells. Z. Juranyi 1 , Z.S. Kocsis 1 , K. Lumniczky 2 , K. Balázs 3 , P. Ágoston 4 , G. Farkas 1 , V. Tölgyesi 1 , G. Székely 1 , T. Major 4 , C. Pesznyák 4 , G. Stelczer 4 , K. Jorgo 4 , L. Gesztesi 4 , C. Polgár 5 , G. Sáfrány 2 1 National Institute of Oncology, Department of Radiobiology and Diagnostic Onco-Cytogenetics, Budapest, Hungary; 2 National Public Health Center , Department of Radiation Medicine, Budapest, Hungary; 3 National Public Health Center, Department of Radiation Medicine, Budapest, Hungary; 4 National Institute of Oncology, Centre of Radiotherapy, Budapest, Hungary; 5 National Institute of Oncology, Semmelweis University, Centre of Radiotherapy, Department of Oncology, Budapest, Hungary Purpose or Objective To perform a detailed analysis of the systemic immune status and change in cytogenetic parameters of prostate cancer patients treated with various radiotherapy protocols in order to mark potential biomarkers for patient follow-up. PO-1827 M1 microglia polarization induced by radiotherapy and dendritic cell immunotherapy combination. V. Pinzi 1,2 , N. Di Ianni 3 , M.L. Fumagalli 4 , M. Maffezzini 3 , L. Fariselli 5 , S. Pellegatta 3 PO-1828 Predictive biomarkers, side effects and tumor control in radiotherapy-treated male cancer patients

Materials and Methods