Immunogenic Cell Death Induction by Ionizing Radiation.

Mengqin Zhu,Mengdie Yang,Xin Fan,Fei Yu,Yuzhen Yin,Jiajia Zhang,Yu Zhang,Han Zhang,Shanshan Qin

doi:10.3389/fimmu.2021.705361

Mengqin Zhu, Mengdie Yang + Show 7 more

Open Access

https://doi.org/10.3389/fimmu.2021.705361

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Abstract

Immunogenic cell death (ICD) is a form of regulated cell death (RCD) induced by various stresses and produces antitumor immunity via damage-associated molecular patterns (DAMPs) release or exposure, mainly including high mobility group box 1 (HMGB1), calreticulin (CRT), adenosine triphosphate (ATP), and heat shock proteins (HSPs). Emerging evidence has suggested that ionizing radiation (IR) can induce ICD, and the dose, type, and fractionation of irradiation influence the induction of ICD. At present, IR-induced ICD is mainly verified in vitro in mice and there is few clinical evidence about it. To boost the induction of ICD by IR, some strategies have shown synergy with IR to enhance antitumor immune response, such as hyperthermia, nanoparticles, and chemotherapy. In this review, we focus on the molecular mechanisms of ICD, ICD-promoting factors associated with irradiation, the clinical evidence of ICD, and immunogenic forms of cell death. Finally, we summarize various methods of improving ICD induced by IR.

Highlights

As a major modality in clinical cancer treatment, radiotherapy (RT) cures or palliates cancer in more than 50% of patients [1]
Nanoparticles are classified into synthetic polymers, biomimetic materials, and inorganic materials according to their physical and chemical properties [80]
The results showed that percentage of tumor-free mice was 100% and enhanced immunogenic cell death (ICD) was verified in tumor tissue featured by increased high mobility group box 1 (HMGB1) release and CRT exposure compared with single treatment

Summary

Introduction

As a major modality in clinical cancer treatment, radiotherapy (RT) cures or palliates cancer in more than 50% of patients [1]. Radiation resistance of some cancers remains a clinical problem [2]. It is urgent to find effective ways to solve this problem. RT utilizes ionizing radiation (IR) to induce cell death directly through damaging double-strand DNA (dsDNA) [1]. IR has the potential to produce antitumor immunity, which is suggested by the discovery of the abscopal effect [3]. IR drives an antitumor immune response through a series of mechanisms [such as the upregulation of major histocompatibility complex (MHC) class I molecules, intercellular adhesion molecule-1, and factor-related apoptosis (Fas)], one of which is the induction of immunogenic cell death (ICD) [5]

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