TY - JOUR
T1 - Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model
AU - Ghaffari-Nazari, Haniyeh
AU - Alimohammadi, Masoumeh
AU - Alimohammadi, Reza
AU - Rostami, Elham
AU - Bakhshandeh, Mohsen
AU - Webster, Thomas J.
AU - Mahmoodi Chalbatani, Ghanbar
AU - Tavakkol-Afshari, Jalil
AU - Amir Jalali, Seyed
N1 - Funding Information:
The authors would like to thank Dr. Seyed Reza Banihashemi (Razi Vaccine and Serum Research Institute, Alborz, Iran) for his precious help in the flow cytometry experiment. We also thank Neda Goharpey (Medical Physicist at the Radiotherapy Department of Shohadaye Tajrish Hospital, Tehran, Iran) for radiotherapy technical support. This study was extracted from the Ph.D. thesis written by Miss. Haniyeh Ghaffari-Nazari was supported by Mashhad University of Medical Sciences (MUMS) with registration number: 970732.
This work was supported by Mashhad University of Medical Sciences (Grant NO: 970732).
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
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 × 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.
KW - Ablative radiotherapy
KW - Abscopal effect
KW - Conventional radiotherapy
KW - Hypofraction radiotherapy
KW - Immune checkpoint inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85127784658&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35417831
U2 - 10.1016/j.intimp.2022.108737
DO - 10.1016/j.intimp.2022.108737
M3 - Article
C2 - 35417831
AN - SCOPUS:85127784658
SN - 1567-5769
VL - 108
JO - International Immunopharmacology
JF - International Immunopharmacology
M1 - 108737
ER -