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Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner

Institute of Anatomy, University of Bern, Baltzerstarsse 2, 3012 Bern, Switzerland
Department of Obstetrics and Gynaecology, Royal Women’s Hospital, University of Melbourne, Melbourne, VIC 3052, Australia
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
Division of Radiation Oncology, Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, VIC 3000, Australia
Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Alexei Gratchev, Alexander N. Orekhov and Evgeny E. Bezsonov
Biomedicines 2022, 10(4), 735;
Received: 15 February 2022 / Revised: 8 March 2022 / Accepted: 18 March 2022 / Published: 22 March 2022
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 2.0)
Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses. View Full-Text
Keywords: microbeam radiotherapy; DNA damage; macrophages; infiltration microbeam radiotherapy; DNA damage; macrophages; infiltration
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MDPI and ACS Style

Trappetti, V.; Fazzari, J.; Fernandez-Palomo, C.; Smyth, L.; Potez, M.; Shintani, N.; de Breuyn Dietler, B.; Martin, O.A.; Djonov, V. Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner. Biomedicines 2022, 10, 735.

AMA Style

Trappetti V, Fazzari J, Fernandez-Palomo C, Smyth L, Potez M, Shintani N, de Breuyn Dietler B, Martin OA, Djonov V. Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner. Biomedicines. 2022; 10(4):735.

Chicago/Turabian Style

Trappetti, Verdiana, Jennifer Fazzari, Cristian Fernandez-Palomo, Lloyd Smyth, Marine Potez, Nahoko Shintani, Bettina de Breuyn Dietler, Olga A. Martin, and Valentin Djonov. 2022. "Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner" Biomedicines 10, no. 4: 735.

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