Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model
Spatially fractionated radiation therapy (SFRT) has a long history of treating bulky and hypoxic tumors. Recent evidence suggests that, compared to conventional uniform dose radiation therapy, SFRT may utilize different mechanisms of tumor cell killing, potentially including bystander and immune-act...
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2025-01-01
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| Online Access: | https://www.mdpi.com/2673-592X/5/1/3 |
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| author | Judith N. Rivera Keith Laemont Artak Tovmasyan Stefan Stryker Kenneth Young Theresa Charity Gregory M. Palmer Sha Chang |
| author_facet | Judith N. Rivera Keith Laemont Artak Tovmasyan Stefan Stryker Kenneth Young Theresa Charity Gregory M. Palmer Sha Chang |
| author_sort | Judith N. Rivera |
| collection | DOAJ |
| description | Spatially fractionated radiation therapy (SFRT) has a long history of treating bulky and hypoxic tumors. Recent evidence suggests that, compared to conventional uniform dose radiation therapy, SFRT may utilize different mechanisms of tumor cell killing, potentially including bystander and immune-activating effects. The abscopal effect in radiation therapy refers to the control or even elimination of distant untreated tumors following the treatment of a primary tumor with radiation, a process believed to be immune-mediated. Such effects have been shown to be enhanced by immunotherapy, particularly immune checkpoint inhibition. In this manuscript, we explore the potential synergy of spatially fractionated radiation therapy, in the form of kV x-ray minibeam, combined with PD-L1 checkpoint inhibition in a murine mammary carcinoma model at conventional dose-rate. We found that minibeam of peak/valley doses of 50 Gy/3.7 Gy performed statistically equivalent but trending better than that of 100 Gy/7.4 Gy in its abscopal effect and so 50 Gy/3.7 Gy was selected for further studies. Our findings indicate that the abscopal effect is significantly greater in the minibeam plus anti-PD-L1 treated animals compared to those receiving uniform dose radiation therapy plus anti-PD-L1 (<i>p</i> = 0.04948). Immune cell profiling in the minibeam plus anti-PD-L1 group compared to uniform dose reveals a consistent trend towards greater immune cell infiltration in the primary tumor, as well as a higher percentage of CD8+ T cells, both systemically and at the abscopal tumor site. |
| format | Article |
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| institution | Kabale University |
| issn | 2673-592X |
| language | English |
| publishDate | 2025-01-01 |
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| series | Radiation |
| spelling | doaj-art-f70b3c3a1c9f4253b6e8a735efa46cc42025-08-20T03:44:04ZengMDPI AGRadiation2673-592X2025-01-0151310.3390/radiation5010003Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma ModelJudith N. Rivera0Keith Laemont1Artak Tovmasyan2Stefan Stryker3Kenneth Young4Theresa Charity5Gregory M. Palmer6Sha Chang7Department of Radiation Oncology, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana 46202, USAClinical & Translational Science Institute, School of Medicine, Duke University, Durham, NC 27710, USADepartment of Translational Neuroscience, Ivy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ 85013, USAMedical Physics Graduate Program, Duke University, Durham, NC 27705, USADepartment of Radiation Oncology, Duke Cancer Institute, Duke University, Durham, NC 27710, USADepartment of Radiation Oncology, Duke Cancer Institute, Duke University, Durham, NC 27710, USAMedical Physics Graduate Program, Duke University, Durham, NC 27705, USADepartment of Biomedical Engineering, A Joint Program of the University of North Carolina-Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USASpatially fractionated radiation therapy (SFRT) has a long history of treating bulky and hypoxic tumors. Recent evidence suggests that, compared to conventional uniform dose radiation therapy, SFRT may utilize different mechanisms of tumor cell killing, potentially including bystander and immune-activating effects. The abscopal effect in radiation therapy refers to the control or even elimination of distant untreated tumors following the treatment of a primary tumor with radiation, a process believed to be immune-mediated. Such effects have been shown to be enhanced by immunotherapy, particularly immune checkpoint inhibition. In this manuscript, we explore the potential synergy of spatially fractionated radiation therapy, in the form of kV x-ray minibeam, combined with PD-L1 checkpoint inhibition in a murine mammary carcinoma model at conventional dose-rate. We found that minibeam of peak/valley doses of 50 Gy/3.7 Gy performed statistically equivalent but trending better than that of 100 Gy/7.4 Gy in its abscopal effect and so 50 Gy/3.7 Gy was selected for further studies. Our findings indicate that the abscopal effect is significantly greater in the minibeam plus anti-PD-L1 treated animals compared to those receiving uniform dose radiation therapy plus anti-PD-L1 (<i>p</i> = 0.04948). Immune cell profiling in the minibeam plus anti-PD-L1 group compared to uniform dose reveals a consistent trend towards greater immune cell infiltration in the primary tumor, as well as a higher percentage of CD8+ T cells, both systemically and at the abscopal tumor site.https://www.mdpi.com/2673-592X/5/1/3radiation therapyimmune therapyminibeam radiation therapyspatially fractionated radiation therapyimmune checkpoint inhibitor |
| spellingShingle | Judith N. Rivera Keith Laemont Artak Tovmasyan Stefan Stryker Kenneth Young Theresa Charity Gregory M. Palmer Sha Chang Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model Radiation radiation therapy immune therapy minibeam radiation therapy spatially fractionated radiation therapy immune checkpoint inhibitor |
| title | Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model |
| title_full | Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model |
| title_fullStr | Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model |
| title_full_unstemmed | Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model |
| title_short | Minibeam Spatially-Fractionated Radiation Therapy Is Superior to Uniform Dose Radiation Therapy for Abscopal Effect When Combined with PD-L1 Checkpoint Inhibitor Immunotherapy in a Dual Tumor Murine Mammary Carcinoma Model |
| title_sort | minibeam spatially fractionated radiation therapy is superior to uniform dose radiation therapy for abscopal effect when combined with pd l1 checkpoint inhibitor immunotherapy in a dual tumor murine mammary carcinoma model |
| topic | radiation therapy immune therapy minibeam radiation therapy spatially fractionated radiation therapy immune checkpoint inhibitor |
| url | https://www.mdpi.com/2673-592X/5/1/3 |
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