Radiotherapy and immune response: the systemic effects of a local treatment

Heloisa de Andrade Carvalho, Rosangela Correa Villar, Heloisa de Andrade Carvalho, Rosangela Correa Villar

Abstract

Technological developments have allowed improvements in radiotherapy delivery, with higher precision and better sparing of normal tissue. For many years, it has been well known that ionizing radiation has not only local action but also systemic effects by triggering many molecular signaling pathways. There is still a lack of knowledge of this issue. This review focuses on the current literature about the effects of ionizing radiation on the immune system, either suppressing or stimulating the host reactions against the tumor, and the factors that interact with these responses, such as the radiation dose and dose / fraction effects in the tumor microenvironment and vasculature. In addition, some implications of these effects in cancer treatment, mainly in combined strategies, are addressed from the perspective of their interactions with the more advanced technology currently available, such as heavy ion therapy and nanotechnology.

Conflict of interest statement

No potential conflict of interest was reported.

Figures

Figure 1
Figure 1
The effects of ionizing radiation effects on the immune system. Either stimulation or suppression of the immune system occurs. Stressed cells may simply undergo anti-inflammatory clearance resulting in non-immunogenic cell death or trigger inflammatory signaling that will release damage-associated molecular patterns (DAMPs) with the activation of dendritic cells that initiate cytotoxic T-cell responses against tumor cells. On the other hand, inactivation of these cells (DCs and cytotoxic T-cells) with the recruitment of MDSCs and T regulator lymphocytes and the secretion of TGF-β leads to the modification of the macrophage phenotype from a pro-inflammatory type M1 to an immunosuppressive type M2 that may allow tumor growth and progression. [Adapted from Derer et al., 2015 and Bockel et al., 2017 93]. Abbreviations: TGF-β, tumor growth factor-β; IL, interleukin; RT, radiotherapy; HSP, heat shock proteins; HMGB1, high mobility group box 1 molecules; ATP, adenosine-5-triphosphate; TNF, tumor necrosis factor; NOS, nitrogen reactive species; DC, dentritic cells; NK, natural killer; MDSC, myeloid derived suppressor cells; Treg, T regulator lymphocyte; TGF-β, tumor growth factor-β; TAM, tumor-associated macrophages.

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