PMID- 35417831 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220623 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 108 DP - 2022 Jul TI - Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model. PG - 108737 LID - S1567-5769(22)00221-1 [pii] LID - 10.1016/j.intimp.2022.108737 [doi] AB - Radiotherapy (RT) can induce immune-mediated responses in local irradiated tumors, and non-irradiated distant metastasis is termed the abscopal effect. Here, we aimed to evaluate the impact of different RT doses and fractions on anti-tumor responses within local irradiated and distance non-irradiated tumor microenvironments. In mice bearing CT26 tumors, the primary tumor was irradiated with three different RT doses (16 Gy x 1F, 10 Gy x 2F, and 3 Gy x 10F) with the same biologically effective dose. Tumor volumes and immune cells changes were assessed in irradiated and non-irradiated tumors. Survival times were evaluated over 90 days. Only 16 Gy x 1F radiation increased CD8 + T cells number in the irradiated (p = 0.043) and non-irradiated (p = 0.047) tumors compared to the untreated group. A high frequency of tumor-associated macrophages-1 (TAM-1) and low TAM-2 was found in 16 Gy x 1F irradiated mice. Moreover, 16 Gy x 1F significantly induced interferon gamma (IFNgamma)-producing CD8 + cells in the spleen compared to controls (p = 0.021). Hypofraction regimens (16 Gy x 1F, 10 Gy x 2F) caused a reduction in myeloid-derived suppressor cells in the irradiated tumors. We detected A modest growth delay in both flank tumors and long-term survival after hypofraction treatments (16 Gy x 1F, 10 Gy x 2F). A single high RT dose increased CD8 + cells number in irradiated (p = 0.000) and non-irradiated (p = 0.002) tumors approximal up to 2 points along with significant induction of IFN-gamma production by CD8 + cells in the spleen when combined with anti- programmed death ligand-1 (PDL-1) (p = 0.000). Combination therapy was also associated with bilateral tumor growth control and increased life span in mice. Hypofractionated RT schedules, especially single high dose, seem the most effective regimen for inducing an abscopal effect. Immune checkpoint inhibitors could promote RT-induced systemic effects. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Ghaffari-Nazari, Haniyeh AU - Ghaffari-Nazari H AD - Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: nazarih931@mums.ac.ir. FAU - Alimohammadi, Masoumeh AU - Alimohammadi M AD - Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: alimohamadi_m@razi.tums.ac.ir. FAU - Alimohammadi, Reza AU - Alimohammadi R AD - Department of Medical Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Rostami, Elham AU - Rostami E AD - Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: RostamiPE941@mums.ac.ir. FAU - Bakhshandeh, Mohsen AU - Bakhshandeh M AD - Department of Radiology Technology, Allied Medical Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: mbakhshandeh@sbmu.ac.ir. FAU - Webster, Thomas J AU - Webster TJ AD - Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA. FAU - Mahmoodi Chalbatani, Ghanbar AU - Mahmoodi Chalbatani G AD - Tumor Immunotherapy and Microenvironment Group, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg. Electronic address: ghanbar.mahmoodichalbatani@lih.lu. FAU - Tavakkol-Afshari, Jalil AU - Tavakkol-Afshari J AD - Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: tavakolaj@mums.ac.ir. FAU - Amir Jalali, Seyed AU - Amir Jalali S AD - Department of Medical Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: jalalia@sbmu.ac.ir. LA - eng PT - Journal Article DEP - 20220410 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 82115-62-6 (Interferon-gamma) RN - EC 3.6.4.6 (N-Ethylmaleimide-Sensitive Proteins) SB - IM MH - Animals MH - *CD8-Positive T-Lymphocytes MH - Cell Line, Tumor MH - Combined Modality Therapy MH - Interferon-gamma MH - Mice MH - N-Ethylmaleimide-Sensitive Proteins MH - *Neoplasms, Experimental/radiotherapy MH - *Radiation Dosage OTO - NOTNLM OT - Ablative radiotherapy OT - Abscopal effect OT - Conventional radiotherapy OT - Hypofraction radiotherapy OT - Immune checkpoint inhibitor EDAT- 2022/04/14 06:00 MHDA- 2022/06/22 06:00 CRDT- 2022/04/13 20:07 PHST- 2021/12/19 00:00 [received] PHST- 2022/03/16 00:00 [revised] PHST- 2022/03/25 00:00 [accepted] PHST- 2022/04/14 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/04/13 20:07 [entrez] AID - S1567-5769(22)00221-1 [pii] AID - 10.1016/j.intimp.2022.108737 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 Jul;108:108737. doi: 10.1016/j.intimp.2022.108737. Epub 2022 Apr 10.