Immunogenic Cell Death Induction by Ionizing Radiation

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.

Aldolase A and Phospholipase D1 Synergistically Resist Alkylating Agents and Radiation in Lung Cancer

“…Oxygen acts as a radiosensitizer (46), but vascular damage caused by radiation can exacerbate tumor hypoxia and lead to HIF-1a dependent consequences (47). Tumor irradiation even induces damage response and leads to the immunogenic cell death (ICD) of cancer cells (48). However, suppressive immune cell enhancement may still limit T-cell activation and checkpoint suppression (49).…”

Narrative Review of Synergistics Effects of Combining Immunotherapy and Stereotactic Radiation Therapy

“…Radiation-induced ICD is essential for the initiation of innate and adaptive immune responses in TME [ 23 , 24 ]. In ICD, distinct molecular events will occur in dying cells that are required.…”

“…As explained above, SRT can induce ICD, TAA release, and increased antigen presentation. DAMPs will allow activation and maturation of DCs that then migrate to the tumor-associated draining lymph nodes [ 23 , 54 ]. In the lymph node, two signals allow efficient activation of T cells.…”

Irradiation immunity interactions

“…For example, RT triggers APC secretion of IL‐1β and IL‐18, critical components of the inflammasome pathway with reported dual roles in tumorigenesis, IL‐1β and IL‐18 can boost T cell activation but also enhance the accumulation of cells with immunosuppressive phenotypes 31,32,89,90 . DAMPs released by irradiated cancer cells can also activate the tumour vasculature endothelium to upregulate cell adhesion molecules—such as ICAM‐1, VCAM‐1 and E‐selectin—and the production of chemoattractants—such as IL‐6, CXCL1, CXCL2, CCL7, CXCL8, CCL2, IL‐1β and G‐CSF 24,38,75,91 . In fact, many of these molecules are reported to have conflicting roles in tumour development because of their pro‐inflammatory functions 89 .…”

“…31,32,89,90 DAMPs released by irradiated cancer cells can also activate the tumour vasculature endothelium to upregulate cell adhesion molecules-such as ICAM-1, VCAM-1 and E-selectin-and the production of chemoattractants-such as IL-6, CXCL1, CXCL2, CCL7, CXCL8, CCL2, IL-1b and G-CSF. 24,38,75,91 In fact, many of these molecules are reported to have conflicting roles in tumour development because of their proinflammatory functions. 89 Although neutrophils are well documented to stimulate tumour progression, 92,93 RTinduced inflammation can result in the recruitment of ROS-producing neutrophils to the TME exacerbating the oxidative stress and promoting apoptosis of cancer cells that may lead to further DAMP release.…”