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

Trappetti, Verdiana; Fazzari, Jennifer; Fernandez-Palomo, Cristian; Smyth, Lloyd; Potez, Marine; Shintani, Nahoko; de Breuyn Dietler, Bettina; Martin, Olga A.; Djonov, Valentin (2022). Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner. Biomedicines, 10(4), p. 735. MDPI 10.3390/biomedicines10040735

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Trappetti, Verdiana, Fazzari, Jennifer Michelina, Fernandez Palomo, Cristian Gabriel, Smyth, Lloyd Mark Lee, Potez, Marine Therese Charlette, Shintani, Nahoko, de Breuyn, Bettina, Martin, Olga Alexeevna, Djonov, Valentin Georgiev

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2227-9059

Publisher:

MDPI

Language:

English

Submitter:

David Christian Haberthür

Date Deposited:

29 Mar 2022 10:41

Last Modified:

05 Dec 2022 16:17

Publisher DOI:

10.3390/biomedicines10040735

BORIS DOI:

10.48350/168195

URI:

https://boris.unibe.ch/id/eprint/168195

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