Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model

Haniyeh Ghaffari-Nazari, Masoumeh Alimohammadi, Reza Alimohammadi, Elham Rostami, Mohsen Bakhshandeh, Thomas J. Webster, Ghanbar Mahmoodi Chalbatani, Jalil Tavakkol-Afshari*, Seyed Amir Jalali*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 × 1F, 10 Gy × 2F, and 3 Gy × 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 × 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 × 1F irradiated mice. Moreover, 16 Gy × 1F significantly induced interferon gamma (IFNγ)-producing CD8 + cells in the spleen compared to controls (p = 0.021). Hypofraction regimens (16 Gy × 1F, 10 Gy × 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 × 1F, 10 Gy × 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-γ 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.

Original languageEnglish
Article number108737
JournalInternational Immunopharmacology
Volume108
Early online date10 Apr 2022
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Ablative radiotherapy
  • Abscopal effect
  • Conventional radiotherapy
  • Hypofraction radiotherapy
  • Immune checkpoint inhibitor

Fingerprint

Dive into the research topics of 'Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model'. Together they form a unique fingerprint.

Cite this