Vitamin A derivative prevents immune cell exhaustion in brain tumours, KAIST study finds

Researchers at KAIST have shown that all-trans retinoic acid (ATRA), a vitamin A metabolite, prevents CD8+ T cells from reaching terminal exhaustion in glioblastoma. The approach could enhance the effectiveness of anti-PD-1 immunotherapy against this notoriously treatment-resistant brain cancer.

Bottom line — ATRA combined with anti-PD-1 improved survival in mouse models of recurrent glioblastoma, per KAIST.

Go deeper (4)

• The research team, led by Professor Heung Kyu Lee, found that ATRA activates WNT/β-catenin signalling in CD8+ T cells and increases the TCF-1βBD protein, which helps maintain T-cell function, according to the study published in Signal Transduction and Targeted Therapy.
• In mouse glioma models, ATRA-treated CD8+ T cells maintained better immune function, reduced tumour burden, and extended survival, the researchers reported.
• Analysis of human glioblastoma data showed that patients with higher retinoic-acid-responsive gene signatures had lower immune cell exhaustion and better overall survival, the team noted.
• The study does not directly demonstrate ATRA's therapeutic efficacy in patients; the researchers emphasised that clinical trials are needed to determine appropriate dosages and combination strategies.

Read the reporting