Glioma-derived S100A9 polarizes M2 microglia to inhibit CD8+T lymphocytes for immunosuppression via αv133 integrin/AKT1/TGF131

作者全名："Huang, Ning; Tang, Jun; Yi, Xiaoyao; Zhang, Maoxin; Li, Bin; Cheng, Yuan; Chen, Jin"

作者地址："[Huang, Ning; Tang, Jun; Yi, Xiaoyao; Zhang, Maoxin; Cheng, Yuan; Chen, Jin] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 2, Chongqing, Peoples R China; [Li, Bin] Chongqing Med Univ, Hlth Minist, Affiliated Hosp 2, Chongqing, Peoples R China; [Li, Bin] Chongqing Gen Hosp, Dept Hlth Management Ctr, Chongqing, Peoples R China; [Chen, Jin] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Chen, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001125537400001

JCR分区：Q2

影响因子：5.1

年份：2024

卷号：1871

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Glioma; Microglial polarization; CD8+T lymphocyte; Immunosuppression

摘要："Our previous studies showed that S100A9 was overexpressed in glioma and promoted tumor growth. However, S100A9 can also be secreted by tumor cells to regulate the tumor microenvironment (TME). In this study, we aimed to explore the functions of glioma derived-S100A9 in microglial M2 polarization, resulting in inhibition of CD8+ T lymphocytes and promotion of immunosuppression. We first showed that glioma exhibited higher expression and secretion of S100A9 than astrocytes. After knocking down S100A9 in two glioma cell lines, the secretion of S100A9 was repressed. Then, the medium was collected and considered as conditioned medium (CM), which was incubated with microglia. We found that glioma-derived S100A9 drove microglial M2 polar-ization and increased TGF131 secretion. These molecular mechanisms were related to the interaction of S100A9 with alpha v133 integrin and the subsequent activation of AKT1 in microglia. Furthermore, we demonstrated that S100A9-induced M2 microglia negatively affected cell viability, IL-2 and IFN-gamma secretion, together with increased early apoptosis in CD8+T lymphocytes via TGF131. Additionally, glioma cells were implanted into mouse brains, and we confirmed that S100A9 stimulated microglial M2 polarization, enhanced TGF131 levels and repressed CD8+ T lymphocytes in orthotopically transplanted tumors. In human glioma samples, S100A9 expression was positively associated with CD206 expression, but negatively correlated with CD8+T lymphocyte accumulation in the TME. Our data indicated that glioma-derived S100A9 has a promising ability to manipulate non-malignant cells and promote immune evasion in the TME, providing valuable insight into the mechanism by which S100A9 participates in the progression of glioma."

基金机构："Chongqing Natural Science Foundation Project [cstc2021jcyj- msxmX0036]; Project of Second Affiliated Hospital of Chongqing Medical University [kryc-yq-2216, kryc-gg-2110]; Chongqing Science and Health Joint Chinese Medicine Research Project [2019ZY023458]; Chunhui Project Foundation of the Education Department of China [HZKY20220218]"

基金资助正文："Chongqing Natural Science Foundation Project (cstc2021jcyj- msxmX0036) , Project of Second Affiliated Hospital of Chongqing Medical University (kryc-yq-2216, kryc-gg-2110) , Chongqing Science and Health Joint Chinese Medicine Research Project (2019ZY023458) . Chunhui Project Foundation of the Education Department of China (HZKY20220218) ."