Immune-Mediated Effects of Microplanar Radiotherapy with a Small Animal Irradiator

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Jan 11

PMID 35008319

Authors

Soha Bazyar

Edward Timothy OBrien 3rd

Thad Benefield

Victoria R Roberts

Rashmi J Kumar

Gaorav P Gupta

Otto Zhou

Yueh Z Lee

Affiliations

Soon will be listed here.

Abstract

Spatially fractionated radiotherapy has been shown to have effects on the immune system that differ from conventional radiotherapy (CRT). We compared several aspects of the immune response to CRT relative to a model of spatially fractionated radiotherapy (RT), termed microplanar radiotherapy (MRT). MRT delivers hundreds of grays of radiation in submillimeter beams (peak), separated by non-radiated volumes (valley). We have developed a preclinical method to apply MRT by a commercial small animal irradiator. Using a B16-F10 murine melanoma model, we first evaluated the in vitro and in vivo effect of MRT, which demonstrated significant treatment superiority relative to CRT. Interestingly, we observed insignificant treatment responses when MRT was applied to Rag and CD8-depleted mice. An immuno-histological analysis showed that MRT recruited cytotoxic lymphocytes (CD8), while suppressing the number of regulatory T cells (Tregs). Using RT-qPCR, we observed that, compared to CRT, MRT, up to the dose that we applied, significantly increased and did not saturate CXCL9 expression, a cytokine that plays a crucial role in the attraction of activated T cells. Finally, MRT combined with anti-CTLA-4 ablated the tumor in half of the cases, and induced prolonged systemic antitumor immunity.

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