Blood Res.  2016 Sep;51(3):157-163. 10.5045/br.2016.51.3.157.

Radiation-induced immune responses: mechanisms and therapeutic perspectives

• Jeong H
• Bok S
• Hong BJ
• Choi HS
• Ahn GO

• KMID: 2353495
• DOI: http://doi.org/10.5045/br.2016.51.3.157

Abstract

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.

Keyword

Radiotherapy; Cancer; Immune system; Hypoxia

MeSH Terms

Anoxia
Cytokines
Hope
Immune System
Immunotherapy
Macrophages
Radiation, Ionizing
Radiotherapy
T-Lymphocytes, Regulatory
Cytokines

Figure

• 

  Fig. 1 Diagram outlining how ionizing radiation (IR) of tumors leads to anti-tumor responses and how tumor hypoxia can interfere such loop. (A) Ionizing radiation can induce anti-tumor immunity via secreting various danger-associated molecular pattern (DAMP) molecules, which can stimulate dendritic cells and cytotoxic T cells. (B) However tumor hypoxia can mediate various pathways, in which can counteract the antitumor immunity.Abbreviations: DCs, dendritic cells; HMGB1, high mobility group protein box 1; ATP, adenosine triphosphate; HSPs, heat shock proteins; HIF-1, hypoxia-inducible factor-1; PD-L1, programmed death-ligand 1; VEGF, vascular endothelial growth factor; VEGFR-1, vascular endothelial growth factor receptor-1; CXCL-12, C-X-C motif chemokine ligand 12; CXCR-4, C-X-C motif chemokine receptor-4; MDSCs, myeloid-derived suppressor cells; TAMs, tumor-associated macrophages; MMP, matrix metalloproteinase; S100A8, S100 calcium-binding protein A8; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α.

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