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Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner
Verdiana Trappetti1, Jennifer Fazzari1, Cristian Fernandez-Palomo1
1Institute of Anatomy, University of Bern, Baltzerstarsse 2, 3012 Bern, Switzerland.
Abstract:
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.
Insights
Microbeam radiation therapy (MRT) uniquely recruits macrophages to radiation-damaged tissues, influencing tumor dynamics and normal tissue responses. This organ-specific macrophage accumulation shows potential for advanced cancer treatment strategies.
Area of Science:
- Oncology
- Radiation Biology
- Immunology
Background:
- Radiation therapy (RT) modulates the immune system, with macrophages playing key roles in tissue repair and tumor progression.
- Microbeam radiation therapy (MRT), a spatially fractionated RT, offers improved tumor control and reduced normal tissue toxicity.
- Understanding MRT's impact on immune cells, particularly macrophages, is crucial for optimizing cancer treatment.
Purpose of the Study:
- To investigate the morphological changes and macrophage infiltration patterns in normal tissues and tumors following MRT.
- To determine if MRT induces organ-specific macrophage accumulation.
- To explore the potential of MRT in modulating the tumor microenvironment and normal tissue responses.
Main Methods:
- Morphological analysis of MRT-irradiated liver, lung, and skin tissues, as well as lung and melanoma tumors.
- Assessment of DNA damage patterns and macrophage infiltration at various time points post-irradiation.
- Characterization of macrophage populations (M1/M2-like) in response to MRT.
Main Results:
- MRT induced distinct DNA damage patterns mirroring the microbeam geometry.
- Macrophages infiltrated MRT-irradiated regions, with timing and extent varying by tissue type (e.g., liver, lung).
- Persistent DNA damage and a geometry-specific influx of M1/M2-like macrophages were observed in lung tumors.
Conclusions:
- MRT has a unique capacity to induce organ- and tissue-specific macrophage accumulation.
- These findings highlight MRT's potential for selective immune cell modulation in cancer therapy.
- Further research is needed to elucidate the roles of these macrophages in normal tissue sparing and anti-tumor immunity.
