Search bioRxiv⌕ Search

Biology subjects

Takata, T.

Publications and source records attributed to Takata, T..

2 recordsLinked to original sources

Boosting Antitumour Efficacy and Immunity by Boron Neutron Capture Therapy with Size-Controlled Nanoparticles

Boron neutron capture therapy (BNCT) is emerging cancer radiotherapy requiring 10B sensitizer. Although boronophenylalanine (BPA)-BNCT is approved clinically in Japan, the low tumour selectivity and retentivity result in the long-time infusion of high doses. Based on our finding of the size-controllable mechanochemical synthesis of boron-10 carbide nanoparticles (10B4C NPs), the 50 nm size NPs grafted with poly(glycerol), {superscript 1}BC(50)-PG, is found to show superior tumour selectivity and retentivity to enhance the eradication efficacy at much lower dosage (5 mg [10B] / kg (mouse)). The dosage is further reduced by twice neutron irradiation or combination with an immune checkpoint inhibitor (ICI). Antitumour immunity is found to be boosted by {superscript 1}BC(50)-PG-BNCT to induce abscopal effect to treat remote or metastatic tumours and long-term memory to prevent cancer recurrence. Additionally, minimal side effects and gradual NP excretion are observed for one year. The 10B4C(50)-PG is concluded to be a promising 10B carrier for clinical application of BNCT due to the prominent antitumour efficacy and immune-activation with minimal toxicity.

cancer biology↗

Glutathione supersulphide regulates T-cell receptor signalling

Immunometabolism regulates functions and fates of immune cells including T cells. Supersulphides, which are universal metabolites containing catenated sulphur atoms, have various physiological functions based on their unique redox properties. Here we found that activation of T-cell receptor (TCR) signalling was accompanied by supersulphide decrease, which suggests a regulatory contribution of sulphur metabolism to immune function. Consistently, inhibiting supersulphide synthesis facilitated TCR activation and exacerbated allergen-induced type 2 inflammation in mice. Supplementation with glutathione trisulphide (GSSSG), a major endogenous supersulphide, suppressed TCR signalling in naive CD4+ T cells and their differentiation and effectively alleviated the inflammation. Docking simulation revealed interaction of GSSSG with CD3{varepsilon} chain in the TCR/CD3 complex, which was supported by mass spectrometry detection of persulphidated glutathionylation at a functionally important CXXC motif of CD3{varepsilon} chain. This study identified a new post-translational modification with supersulfides and demonstrated a critical contribution of sulphur metabolism to TCR signalling regulation.

biochemistry↗