Available online 30 January 2023

Author links open overlay panelAbstract

Macrophages are a vital part of the innate immune system that are involved in healthy biological processes but also in disease modulation and response to therapy. Ionizing radiation is commonly used in the treatment of cancer and, in a lower dose range, as additive therapy for inflammatory diseases. In general, lower doses of ionizing radiation are known to induce rather anti-inflammatory responses, while higher doses are utilized in cancer treatment where they result, next to tumor control, in rather inflammatory responses. Most experiments that have been carried out in ex vivo on macrophages find this to be true, however in vivo, tumor-associated macrophages, for example, show a contradictory response to the respective dose-range. While some knowledge in radiation-induced modulations of macrophages has been collected, many of the underlying mechanisms remain unclear. Due to their pivotal role in the human body, however, they are a great target in therapy and could potentially aid in better treatment outcome. We therefore summarized the current knowledge of macrophage mediated radiation responses.

Section snippetsMacrophage polarization and functionality

Macrophages are an important component of the innate immune system. They are present in most compartments of the body and play a role in most aspects of human biology (Pei and Yeo, 2016). Not only under physiological conditions, but also in disease and subsequent treatments as they can have a positive and negative influence on treatment effectiveness, as e.g., in tumor treatment with radiotherapy (Conrad et al., 2009). In general, macrophages are among the first cells at the site of infection,

Macrophages in health and disease

As mentioned above, macrophages are among the first cells at site of inflammation that are responsible for the destruction of the inflammatory stimuli as well as clearing of dead (immune) cells, especially neutrophils. The acquired antigens of the cause of inflammation (e.g., pathogens) are then presented to T cells, thus bridging the innate immune system with the adaptive immune system. During the course of inflammation Macrophage activity is then switched from a rather inflammatory to an

Molecular effects of ionizing radiation on macrophages

Cancer is often associated with chronic inflammatory conditions and radiotherapy is an important pillar of multimodal cancer therapy, with roughly 60% of all cancer patients undergoing RT at some point over the course of their treatment. In this setting, pro-inflammatory effects such as the induction of immunogenic cell death and acute inflammation is the desired outcome. Nevertheless, a large number of patients also undergoes RT with low doses of X-rays (single doses of 0.5–1.0 Gy with total

Outlook

While many effects of ionizing radiation on macrophages have been unraveled in the past, more research is needed in order to elucidate the molecular facts. For this, sophisticated approaches should take various factors such as radiosensitivity properties of utilized models, radiation quality, inflammatory background, sex and age into consideration. These conditions should play additional roles in the well-known macrophage heterogeneity. In that matter, it has already been shown that age, for

Conclusion

Macrophages are a very heterogeneous cell type with great plasticity and a plethora of functions and abilities depending on the activating stimulus. They are a rather radioresistant cell type that is thus able to be modulated by various doses of ionizing radiation. Depending on the applied dose and fractionation, they subsequently either exert pro- or anti-inflammatory and/or pro- or anti-tumorigenic functions. Thus, no generalized statement on specific radiation-induced modulations can be

Acknowledgments

This work was funded by the Bundesministerium für Bildung und Forschung (BMBF; TOGETHER 02NUK073; GREWIS, 02NUK017G and GREWIS-alpha, 02NUK050E).

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