CELL INTELLIGENCE · 肿瘤细胞治疗研究

Glioblastoma (GBM) is the most malignant primary central nervous system tumor in adults, with strong invasiveness, high recurrence, and poor prognosis. Natural killer (NK) cells, innate immune cells that eliminate glioma stem cells without MHC matching, show promise for GBM immunotherapy, but their efficacy is limited by GBM's immunosuppressive tumor microenvironment (TME), especially via protein post-translational modifications (PTMs).

This review summarizes seven key PTMs' (phosphorylation, acetylation, glycosylation, methylation, ubiquitination, SUMOylation, lactylation) dual regulation on NK cell therapy: physiological PTMs enhance NK cytotoxicity, targeting, and persistence; aberrant PTMs block NK activation, induce exhaustion, and promote GBM immune escape.

It also analyzes bottlenecks (insufficient NK activity/persistence, GBM's PTM-mediated escape) and breakthroughs (PTM-targeted small molecules like TAK-981, CRISPR-edited NK cells, combination therapies). Future directions include BBB precision delivery, PTM-guided personalized therapy, and PTM crosstalk research, aiming to advance NK therapy's clinical translation for GBM.