High linear energy transfer carbon-ion irradiation increases the release of the immune mediator high mobility group box 1 from human cancer cells

Abstract

Anti-tumor immunity modulates the local effects of radiation therapy. High mobility group box 1 (HMGB1) plays a pivotal role in activating antigen-specific T-cell responses. Here, we examined the relationship between linear energy transfer (LET) and HMGB1 release. We assessed the proportions of KYSE-70, HeLa and SiHa cells surviving after carbon-ion (C-ion) beam irradiation with different LET values, using a clonogenic assay. The D10, the dose at which 10% of cells survived, was calculated using a linear–quadratic model. HMGB1 levels in the culture supernatants of C-ion beam–irradiated tumor cells were assessed by enzyme-linked immunosorbent assay. The D10 doses for 13 keV/μm of C-ion irradiation in KYSE-70, HeLa and SiHa cells were 2.8, 3.9 and 4.1 Gy, respectively, whereas those for 70 keV/μm C-ion irradiation were 1.4, 1.9 and 2.3 Gy, respectively. We found that 70 keV/μm of C-ion irradiation significantly increased HMGB1 levels in the culture supernatants of all cell lines 72 h after irradiation compared with non-irradiated controls. Furthermore, 70 keV/μm of C-ion irradiation significantly increased HMGB1 levels in the culture supernatants of all cell lines 72 h after irradiation compared with 13 keV/μm. The results suggest that HMGB1 release from several cancer cell lines increases with increased LET.

The Reciprocity between Radiotherapy and Cancer Immunotherapy

“…The prophagocytic effect of radiation is mediated by the release of damage-associated molecular pattern (DAMP) by tumor cells upon irradiation, including the translocation of the ER chaperone calreticulin, to the cell membrane. This immunogenic cell death process is also characterized by the release of high mobility group box 1 (HMGB1) and ATP, which together promotes tumor cell phagocytosis by macrophages and dendritic cells (20,21). These immune-modulatory effects of radiation appear to be further augmented when it is combined with immune checkpoint blockers (22,23).…”

Glycyrrhizin mitigates radiation‐induced acute lung injury by inhibiting the HMGB1/TLR4 signalling pathway

“…An increasing number of reports have confirmed the functions of HMGB1 in infectious and sterile inflammation, and many therapies targeting HMGB1 have been developed . Some studies reported that radiation could lead to HMGB1 translocation and release, but its role in RILI has not been explicitly revealed …”

“…11,12 Some studies reported that radiation could lead to HMGB1 translocation and release, but its role in RILI has not been explicitly revealed. 13,14 Glycyrrhizin (GL), a glycoconjugated triterpene extracted from the roots and rhizomes of liquorice, has been widely used in Japan and China as a hepatic protector and anti-inflammatory agent for decades. GL has been shown to be a natural inhibitor of HMGB1 by binding to the HMGB1 protein directly and inhibiting its biological activity.…”

Characteristics of PSA Bounce after Radiotherapy for Prostate Cancer: A Meta-Analysis

“…Evidence suggests that a high, single-fractionated dose induces antitumor immunity efficiently [ 57 ], partially by promoting DNA damage response signaling [ 58 ]. In addition, the properties of carbon ions as high linear energy transfer radiation to efficiently induce antitumor immunity (e.g., induction of HMGB1 [ 59 ], OX40L, CD40, ICAM-1, and MHC-1, and suppression of PD-L1 [ 60 ]) might contribute to the high bounce rate for CIRT. Another possible explanation for the higher bounce rate associated with brachytherapy, SBRT, and CIRT is that the highly concentrated doses delivered by these modalities destroy the normal prostate glands more efficiently.…”