Prospects and applications of NK therapy in the treatment of gliomas (Review)

Abstract

Brain tumours are in the spotlight of oncology research due to their intractability and resistance to conventional treatments. High‑risk craniotomies must be performed on patients during tumour resection surgeries due to the specificity of the brain structure, and the complexity of the brain structure also leads to the fact that brain tumours usually cannot be removed completely. Besides, the inability of foreign small molecules to cross the blood‑brain barrier has led to the inability of conventional drug therapy to reach the tumour location in the brain. Furthermore, the damage to healthy brain tissue caused by conventional radiotherapy cannot be ignored. Therefore, brain tumours represented by gliomas are in urgent need for a novel therapeutic approach. Glioma is the most common brain tumour, accounting for 81% of malignant tumours in the central nervous system, and is characterized by high morbidity, recurrence, mortality and low cure rate. In recent years, natural killer (NK) cell immunotherapy for gliomas has gradually emerged and numerous studies have shown surprising therapeutic effects. NK cells have been demonstrated to traverse the blood‑brain barrier and numerous studies have confirmed their ability to kill glioma cells both in vivo and in vitro. This article begins by introducing conventional therapies for glioma, followed by an overview of the potential of NK cell‑based immunotherapy in glioma treatment and the regulatory mechanisms of NK cells within the glioma immune microenvironment. It then summarizes preclinical studies on CAR‑NK cells and clinical advancements in NK cell therapy for glioma. Finally, the paper discusses recent progress in immunotherapy for gliomas and explores novel therapeutic strategies combining NK cell immunotherapy with other treatment modalities.

Keywords: NK cell; cancer; cell therapy; glioma; immunotherapy.

Figure 1.

Receptor interactions between NK cells and tumour cells. Natural cytotoxic receptors on NK cells, such as NCR, CD16 and NKG2D, stimulate NK activation by binding to the corresponding ligands on tumours. CD16, encoded by the FCGR3A gene, interacts with IgG to help NK cells recognise IgG-bound cells, thus exerting antibody-dependent cell-mediated cytotoxicity. NKG2D, encoded by the KLRK1 gene, binds to the NK cell surface connexin DAP10 to stabilise the receptor complex. The suppressive receptors NKG2A, PDL1 and CD155 bind to the corresponding ligands to initiate NK cell inhibition. TIGIT, T-cell immunoreceptor with Ig and ITIM domains; CD16, cluster of differentiation 16; NKG2A-HLA, natural killer group 2A-human leukocyte antigen; CD226/CD96-CD155, cluster of differentiation 226/cluster of differentiation 96-cluster of differentiation 155; NKG2D, natural killer group 2D; CD161-LLT1, cluster of differentiation 161-lectin-like transcript 1; PDL1, programmed death ligand 1; PD1, programmed cell death protein 1; IgG, immunoglobulin G; NK, natural killer.