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Dual Regulation of Post-Translational Modification of Proteins: Bottlenecks and Breakthroughs in NK Cell Therapy for
Yushu Liu1, Qingya Qiu1, Hui Deng1
1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Abstract:
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.
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