Journal article
β2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages
Cancer research (Chicago, Ill.), Vol.82(18), pp.3321-3334
09/16/2022
DOI: 10.1158/0008-5472.CAN-22-0507
PMID: 35841593
Abstract
beta 2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGF beta 1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.
Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that beta 2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-beta 1 (TGF beta 1). Inhibition of B2M attenuated GSC survival, self-renewal, and tumor growth. B2M-induced TGF beta 1 secretion activated paracrine SMAD and PI3K/AKT signaling in TAMs and promoted an M2-like macrophage phenotype. These findings reveal tumor-promoting functions of B2M and suggest that targeting B2M or its downstream axis may provide an effective approach for treating GBM.Significance: beta 2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGF beta 1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.
Details
- Title: Subtitle
- β2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages
- Creators
- Daqi Li - Nanjing Medical UniversityQian Zhang - Nanjing Medical UniversityLu Li - Nanjing Medical UniversityKexin Chen - Nanjing Medical UniversityJunlei Yang - Nanjing Medical UniversityDeobrat Dixit - University of California San DiegoRyan C. Gimple - Case Western Reserve UniversityShusheng Ci - Nanjing Medical UniversityChenfei Lu - Nanjing Medical UniversityLang Hu - Nanjing Medical UniversityJiancheng Gao - Nanjing Medical UniversityDanyang Shan - Nanjing Medical UniversityYangqing Li - Model Animal Research CenterJunxia Zhang - Nanjing Medical UniversityZhumei Shi - Nanjing Medical UniversityDanling Gu - Nanjing Medical UniversityWei Yuan - Yancheng First People's HospitalQiulian Wu - University of California San DiegoKailin Yang - Cleveland ClinicLinjie Zhao - University of California San DiegoZhixin Qiu - University of California San DiegoDeguan Lv - University of California San DiegoWei Gao - Nanjing Medical UniversityHui Yang - Huashan HospitalFan Lin - Nanjing Medical UniversityQianghu Wang - Jiangsu Cancer HospitalJianghong Man - National Center of Biomedical AnalysisChaojun Li - Nanjing UniversityWeiwei Tao - Huazhong Agricultural UniversitySameer Agnihotri - University of PittsburghXu Qian - Jiangsu Cancer HospitalYu Shi - Ministry of Education of the People's Republic of ChinaYongping You - Jiangsu Province HospitalNu Zhang - The First Affiliated Hospital, Sun Yat-sen UniversityJeremy N. Rich - University of California San DiegoXiuxing Wang - University of California San Diego
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.82(18), pp.3321-3334
- DOI
- 10.1158/0008-5472.CAN-22-0507
- PMID
- 35841593
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 14
- Grant note
- 81822033 / National Natural Science Outstanding Youth Foundation of China; National Natural Science Foundation of China (NSFC) National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 2016YFA0503000 / National Natural Science Outstanding Youth Foundation of China; National Natural Science Foundation of China (NSFC) 81572477; 81772683; 82072779 / National Key Research and Development Program of China
- Language
- English
- Date published
- 09/16/2022
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696561102771
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