文献类型：期刊文献

英文题名：Natural killer cell dysfunction in glioma: from immune evasion to immunotherapy

作者：Zhang, Run[1];Ma, Pengcheng[2];Tang, Ke[2];Cao, Yanchun[1];Yang, Yani[1];Hao, Shengyang[1];Li, Tingting[3];Peng, Xiaoming[2]

第一作者：张蕊

通信作者：Peng, XM[1]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Affiliated Hosp, Dept Neurol, Lanzhou, Gansu, Peoples R China;[3]Lanzhou Second Peoples Hosp, Dept Psychiat, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp, Dept Neurol, Lanzhou, Gansu, Peoples R China.|[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;[10735]甘肃中医药大学;

年份：2026

卷号：17

起止页码：1787023.0

外文期刊名：FRONTIERS IN IMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-105034957010);WOS:【SCI-EXPANDED(收录号:WOS:001729953600001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. This work was supported by Project of Gansu Provincial Administration of Chinese Medicine (GZKG-2024-59), Natural Science Foundation of Gansu Province (24JRRA1039). Gansu Province science and technology plan project (22JR11RA127) Innovation Program for Young Scientific and Technological Talents of Lanzhou City (2024-QN-124).

语种：英文

外文关键词：CAR-NK therapy; glioblastoma; immune checkpoint inhibition; immune evasion; immunosuppression; natural killer cell; tumormicroenvironment

摘要：Natural killer (NK) cells, critical components of innate immunity, possess the ability to eliminate tumor cells without prior sensitization. In gliomas, particularly glioblastoma, the tumor microenvironment (TME) exerts potent immunosuppressive effects that impair NK cell function through MHC-I overexpression, secretion of TGF-beta and IDO, and recruitment of myeloid-derived suppressor cells (MDSCs). Emerging evidence highlights the significance of NK cell infiltration, cytotoxicity, and ligand-receptor dynamics-such as NKG2D, KIRs, and CX3CR1+ subsets-in shaping prognosis and therapeutic responsiveness in glioma patients. Therapeutic strategies including activation of NK cells via chemotherapeutics (bortezomib, decitabine), blockade of inhibitory receptors (NKG2A, CD161), and combinatorial approaches with immune checkpoint inhibitors are under active investigation. Notably, chimeric antigen receptor (CAR)-engineered NK cells targeting EGFR, HER2, GD2, and CD133 show promise in preclinical glioma models due to their enhanced specificity and reduced toxicity compared to CAR-T cells. This review summarizes the multifaceted roles of NK cells in glioma immunity and highlights novel immunotherapeutic strategies to restore NK cell function and improve clinical outcomes.