Article
Multidisciplinary Sciences
Qing Guo, Shuai Shen, Gefei Guan, Chen Zhu, Cunyi Zou, Jingyuan Cao, Wen Cheng, Xiaoyan Xu, Juanhan Yu, Zhiguo Lin, Guoli Wang, Ling Chen, Peng Cheng, Anhua Wu
Summary: Glioblastoma (GBM) shares common signaling pathways involving TIM-3, an immune checkpoint, between tumor and non-tumor cells. The study reveals that TIM-3 in glioma cells not only regulates the malignant behaviors of glioma cells but also induces macrophage migration and transition to an anti-inflammatory/protumorigenic phenotype through the TIM-3/IL6 signal. Blocking this feedback loop may provide a novel therapeutic strategy for GBM.
Article
Engineering, Environmental
Xuefeng Zhang, Qing Guo, Zongren Zhao, Peng Cheng, Anhua Wu, Hongmei Liu
Summary: A new therapeutic strategy combining anticancer drugs and immunotherapy was developed to target tumor-associated macrophages and glioma stem cells, leading to inhibited tumor growth and prolonged survival in a mouse model of glioblastoma. These findings highlight the importance of this approach for the treatment of glioblastoma.
CHEMICAL ENGINEERING JOURNAL
(2023)
Review
Immunology
Guoqing Wang, Kunhong Zhong, Zeng Wang, Zongliang Zhang, Xin Tang, Aiping Tong, Liangxue Zhou
Summary: This review discusses the characteristics and functions of TAMs in GBM, and evaluates the current state of TAMs-targeting strategies. TAMs are logical therapeutic targets for GBM, and understanding how TAMs promote GBM progression is of great significance for new immune therapeutic approaches for GBM patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Casper J. Pachocki, Elly M. Hol
Summary: DMG is a highly malignant pediatric brain tumor with a near-zero survival rate. Recent advances in research have revealed that DMG and GBM are distinct disease entities, with separate tissue characteristics and genetic profiles. DMG has a unique immune microenvironment, characterized by low levels of immune cell infiltration, inflammation, and immunosuppression that may impact disease development and outcome.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Cell Biology
Stephanie Sanders, Denise M. Herpai, Analiz Rodriguez, Yue Huang, Jeff Chou, Fang-Chi Hsu, Darren Seals, Ryan Mott, Lance D. Miller, Waldemar Debinski
Summary: The study indicates that high expression of ALDH1A2 in the GBM microenvironment, especially in M2 GAM, may promote the progression of GBM. The expression of ALDH1A2 is increased upon tumor recurrence and plays a crucial role in regulating the activity of macrophages.
Article
Oncology
Tadas K. Rimkus, Austin B. Arrigo, Dongqin Zhu, Richard L. Carpenter, Sherona Sirkisoon, Daniel Doheny, Angelina T. Regua, Grace L. Wong, Sara Manore, Calvin Wagner, Hui-Kuan Lin, Guangxu Jin, Jimmy Ruiz, Michael Chan, Waldemar Debinski, Hui-Wen Lo
Summary: The study found that TUSC2 protein expression is reduced in glioblastoma compared to normal brain due to protein destabilization. NEDD4-mediated polyubiquitination is a novel mechanism for TUSC2 degradation in glioblastoma. TUSC2 loss promotes glioblastoma progression through upregulation of Bcl-xL and its knockout gene signature predicts poor patient survival.
Article
Cell Biology
Lizhi Pang, Madeline Dunterman, Wenjing Xuan, Annette Gonzalez, Yiyun Lin, Wen-Hao Hsu, Fatima Khan, Robert S. Hagan, William A. Muller, Amy B. Heimberger, Peiwen Chen
Summary: It has been found that the clock gene regulates the activity of glioma stem cells and affects the development of glioblastoma. The clock gene directs the expression of OLFML3, which leads to the upregulation of POSTN through HIF1a and subsequently promotes tumor angiogenesis through activation of the TBK1 signaling pathway. Blocking the CLOCK-directed POSTN-TBK1 axis has been shown to inhibit tumor progression and angiogenesis.
Article
Chemistry, Multidisciplinary
Ruiqi Li, Lian Chen, Qin Ji, Qing Liang, Ying Zhu, Wei Fu, Tianyou Chen, Hongwei Duan, Wenshan He, Zushun Xu, Xiaofang Dai, Jinghua Ren
Summary: Radiotherapy is a crucial treatment for glioblastoma patients, but recurrence is inevitable. Tumor evolution and the acquisition of radioresistance hinder the efficacy of radiotherapy. Understanding the mechanisms of tumor subclonal evolution can lead to the development of new strategies.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Review
Oncology
Weiqiong Zhang, Ruiping Zhou, Xin Liu, Lin You, Chang Chen, Xiaoling Ye, Jie Liu, Youde Liang
Summary: Cancer stem cells (CSCs) and exosomes derived from M2 macrophages play crucial roles in cancer development and progression. Exosomes influence immune responses and may serve as markers for cancer diagnosis and prognosis. Understanding the role of exosomes in CSCs could lead to the development of new diagnostic tools and treatments.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jennifer K. Matsui, Haley K. Perlow, Alex R. Ritter, Rituraj Upadhyay, Raju R. Raval, Evan M. Thomas, Sasha J. Beyer, Clement Pillainayagam, Justin Goranovich, Shirley Ong, Pierre Giglio, Joshua D. Palmer
Summary: This review discusses the treatment modalities for glioblastoma, the mechanisms of radioresistance, and promising radiosensitizers. Small molecules and immunotherapy agents used in conjunction with radiotherapy have been studied in clinical trials. Recent preclinical studies regarding radiosensitizers for glioblastoma are also discussed.
Article
Neurosciences
Yuyang Liu, Ying Shi, Mengwan Wu, Jialin Liu, Hong Wu, Chuan Xu, Ling Chen
Summary: PGCCs promote malignancy and immune-suppressive microenvironment in GBM. PGCCs or their progeny cells may be a potential therapeutic target for GBM.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Eilam Yeini, Paula Ofek, Sabina Pozzi, Nitzan Albeck, Dikla Ben-Shushan, Galia Tiram, Sapir Golan, Ron Kleiner, Ron Sheinin, Sahar Israeli Dangoor, Shlomit Reich-Zeliger, Rachel Grossman, Zvi Ram, Henry Brem, Thomas M. Hyde, Prerna Magod, Dinorah Friedmann-Morvinski, Asaf Madi, Ronit Satchi-Fainaro
Summary: The study revealed the crucial role of P-selectin in promoting GB proliferation and invasion, showing that inhibiting P-selectin could reduce tumor growth and increase survival in mouse models. The findings shed light on the function of tumor-associated microglia/macrophages and the mechanisms by which GB cells suppress the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Emily E. S. Brettschneider, Masaki Terabe
Summary: Glioblastoma is an aggressive and deadly cancer, and immunotherapies have not made significant progress. NKT cells may play a key immunoregulatory role in glioblastoma, but their specific function is still unclear.
Review
Immunology
Nian Chen, Cheng Peng, Dan Li
Summary: Glioblastoma (GBM) is the most common malignant brain tumor in adults. The inflammatory microenvironment accelerates epigenetic changes in GBM and helps tumors evade immune surveillance. GBM tumor cells and glioma-associated microglia/macrophages are the primary contributors, and the modification of epigenetic events exacerbates the proliferation, invasion, and migration of GBM. Certain drugs can reverse the inflammatory environment and inhibit GBM growth and invasion.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell & Tissue Engineering
Gui-Long Zhang, Chuan-Fang Wang, Cheng Qian, Yun-Xiang Ji, Ye-Zhong Wang
Summary: Glioblastoma multiforme (GBM), the most common malignant brain tumor in adults, is mostly untreatable with poor prognosis and low survival rates. Communication between GBMs and non-glioma cells in the tumor microenvironment, as well as the involvement of neural stem cells in the subventricular zone, play crucial roles in tumor growth and recurrence. Understanding the interactions between glioma and neural stem cells may lead to new therapeutic strategies for GBM.
WORLD JOURNAL OF STEM CELLS
(2021)
Article
Cell Biology
Deobrat Dixit, Briana C. Prager, Ryan C. Gimple, Tyler E. Miller, Qiulian Wu, Shira Yomtoubian, Reilly L. Kidwell, Deguan Lv, Linjie Zhao, Zhixin Qiu, Guoxin Zhang, Derrick Lee, Donglim Esther Park, Robert J. Wechsler-Reya, Xiuxing Wang, Shideng Bao, Jeremy N. Rich
Summary: In this study, DPY30 was identified as an in vivo-specific glioblastoma dependency using in vivo genetic screening. By examining the chromatin characteristics of glioblastoma stem cells, DPY30 was found to regulate angiogenesis and hypoxia pathways critical for tumor growth. However, DPY30 was dispensable in vitro. Additionally, DPY30 was shown to regulate the downstream effector PDE4B, with the inhibitor rolipram preferentially targeting DPY30-expressing cells and impairing the growth of patient-derived xenograft tumors in mice.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Zhixin Qiu, Linjie Zhao, Jia Z. Shen, Zhengyu Liang, Qiulian Wu, Kailin Yang, Lihua Min, Ryan C. Gimple, Qiyuan Yang, Shruti Bhargava, Chunyu Jin, Cheryl Kim, Denise Hinz, Deobrat Dixit, Jean A. Bernatchez, Briana C. Prager, Guoxin Zhang, Zhen Dong, Deguan Lv, Xujun Wang, Leo J. Y. Kim, Zhe Zhu, Katherine A. Jones, Ye Zheng, Xiuxing Wang, Jair L. Siqueira-Neto, Lukas Chavez, Xiang-Dong Fu, Charles Spruck, Jeremy N. Rich
Summary: This study identifies the YY1-CDK9 transcription elongation complex as a crucial factor in maintaining glioblastoma stemness and therapeutic resistance. Targeting this complex can activate interferon response, reduce regulatory T-cell infiltration, and enhance the efficacy of immune checkpoint therapy.
Article
Oncology
Daqi Li, Qian Zhang, Lu Li, Kexin Chen, Junlei Yang, Deobrat Dixit, Ryan C. Gimple, Shusheng Ci, Chenfei Lu, Lang Hu, Jiancheng Gao, Danyang Shan, Yangqing Li, Junxia Zhang, Zhumei Shi, Danling Gu, Wei Yuan, Qiulian Wu, Kailin Yang, Linjie Zhao, Zhixin Qiu, Deguang Lv, Wei Gao, Hui Yang, Fan Lin, Qianghu Wang, Jianghong Man, Chaojun Li, Weiwei Tao, Sameer Agnihotri, Xu Qian, Yu Shi, Yongping You, Nu Zhang, Jeremy N. Rich, Xiuxing Wang
Summary: The study reveals the tumor-promoting functions of B2M in glioblastoma and suggests potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment. B2M activation leads to the maintenance of stem-like neoplastic populations and induces an anti-inflammatory state, while promoting the polarization of macrophages towards an M2-like phenotype. Inhibition of B2M could attenuate glioblastoma stem cell survival, self-renewal, and tumor growth.
Article
Cell Biology
Deguan Lv, Ryan C. Gimple, Cuiqing Zhong, Qiulian Wu, Kailin Yang, Briana C. Prager, Bhaskar Godugu, Zhixin Qiu, Linjie Zhao, Guoxin Zhang, Deobrat Dixit, Derrick Lee, Jia Z. Shen, Xiqing Li, Qi Xie, Xiuxing Wang, Sameer Agnihotri, Jeremy N. Rich
Summary: Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. PDGF signaling induces m(6)A accumulation in GBM stem cells to regulate mitophagy. PDGF-METTL3-OPTN signaling is identified as a therapeutic target for GBM treatment.
DEVELOPMENTAL CELL
(2022)
Article
Oncology
Mengjie Zhao, Yanhui Li, Chenfei Lu, Fangshu Ding, Miao Xu, Xin Ge, Mengdie Li, Zhen Wang, Jianxing Yin, Junxia Zhang, Xiefeng Wang, Zehe Ge, Hong Xiao, Yong Xiao, Hongyi Liu, Wentao Liu, Yuandong Cao, Qianghu Wang, Yongping You, Xiuxing Wang, Kun Yang, Zhumei Shi, Xu Qian
Summary: Radiotherapy resistance in gliomas is a major concern. This study identified that mitochondrial metabolic pathways are suppressed in radioresistant gliomas. Decreased expression of PGC1a, a key regulator of mitochondrial biogenesis and metabolism, correlated with glioma recurrence and predicted poor prognosis and response to radiotherapy. Restoring PGC1a activity increased radiosensitivity of resistant glioma cells.
Article
Oncology
Min Wu, Lingxiang Wu, Wei Wu, Mengyan Zhu, Jianyu Li, Ziyu Wang, Jie Li, Rong Ding, Yuan Liang, Liangyu Li, Tingting Zhang, Bin Huang, Yun Cai, Kening Li, Lu Li, Rui Zhang, Baoli Hu, Fan Lin, Xiuxing Wang, Siyuan Zheng, Jian Chen, Yongping You, Tao Jiang, Junxia Zhang, Hongshan Chen, Qianghu Wang
Summary: Tumor-associated macrophages (TAM) play a crucial role in immunosuppression, but how TAMs are transformed and influence the tumor microenvironment (TME) is not fully understood. In this study, researchers identified a subset of TAMs termed double-positive TAMs that co-expressed macrophage and tumor markers. These double-positive TAMs had immunosuppressive phenotypes and were transformed into M2-like macrophages, expressing immune-checkpoint proteins and suppressing T cell proliferation. This study sheds light on the processes driving TAM-mediated immunosuppression in glioblastoma.
Article
Oncology
Weiwei Tao, Hong Lei, Wenlong Luo, Zhi Huang, Peng Ling, Mengyue Guo, Lihao Wan, Kui Zhai, Qian Huang, Qiulian Wu, Shutong Xu, Liang Zeng, Xiuxing Wang, Zhiqiang Dong, Jeremy N. Rich, Shideng Bao
Summary: In this study, the novel INHAT repressor (NIR) was found to promote ribosomal DNA transcription, supporting the proliferation of glioma stem cells (GSCs) and the growth of glioblastoma (GBM). High expression of NIR predicts poor survival in GBM patients, and disruption of NIR inhibits GSC proliferation and tumor growth. Mechanistically, NIR activates rDNA transcription by cooperating with Nucleolin and Nucleophosmin 1, important nucleolar transcription factors.
Article
Oncology
Zengpanpan Ye, Xiaolin Ai, Kailin Yang, Zhengnan Yang, Fan Fei, Xiaoling Liao, Zhixin Qiu, Ryan C. Gimple, Huairui Yuan, Hao Huang, Yanqiu Gong, Chaoxin Xiao, Jing Yue, Liang Huang, Olivier Saulnier, Wei Wang, Peidong Zhang, Lunzhi Dai, Xin Wang, Xiuxing Wang, Young Ha Ahn, Chao You, Jianguo Xu, Xiaoxiao Wan, Michael D. Taylor, Linjie Zhao, Jeremy N. Rich, Shengtao Zhou
Summary: Single-cell sequencing of glioblastoma tumor immune microenvironment (TIME) revealed that oxidative stress induces NR4A2-dependent transcriptional activity in microglia. Inhibition of NR4A2 or SQLE enhances the efficacy of immune-checkpoint blockade in GBM. Metabolic reprogramming of microglia informs synergistic vulnerabilities for immune-checkpoint blockade therapy in this immunologically cold brain tumor.
Article
Oncology
Nunu Huang, Zhipeng Chen, Xuesong Yang, Yixin Gao, Jian Zhong, Yan Li, Feizhe Xiao, Xiuxing Wang, Yu Shi, Nu Zhang
Summary: The micropeptide MP31, translated from the PTEN uORF and localized in mitochondria, disrupts the mitochondrial quality control process and inhibits GBM tumorigenesis. MP31 induces MMP loss, triggers mitochondrial fission, and blocks mitophagic flux, resulting in the accumulation of damaged mitochondria and the production of reactive oxygen species and DNA damage. Furthermore, MP31 enhances the sensitivity of GBM cells to chemotherapy without inducing toxicity in normal cells.
Article
Oncology
Danling Gu, Fengqi Zhou, Hao You, Jiancheng Gao, Tao Kang, Deobrat Dixit, Qiulian Wu, Kailin Yang, Shusheng Ci, Danyang Shan, Xiao Fan, Wei Yuan, Qian Zhang, Chenfei Lu, Daqi Li, Ningwei Zhao, Zhumei Shi, Wei Gao, Fan Lin, Jianghong Man, Qianghu Wang, Xu Qian, Stephen C. Mack, Weiwei Tao, Sameer Agnihotri, Nu Zhang, Yongping You, Jeremy N. Rich, Junxia Zhang, Xiuxing Wang
Summary: This study investigates the adaptive behavior of glioblastoma stem cells (GSCs) under different cholesterol supplies and finds that cholesterol biosynthetic enzymes are expressed at higher levels in the tumor core than in the invasive margins. The transcription factor SREBP2 promotes cholesterol biosynthesis, proliferation, self-renewal, and tumor growth in GSCs, and regulates the balance between cholesterol biosynthesis and uptake in different nutrient conditions. These findings provide important insights for a novel treatment strategy for glioblastoma.
Article
Oncology
Qian Huang, Liping Liu, Dakai Xiao, Zhi Huang, Wenjun Wang, Kui Zhai, Xiaoguang Fang, Jongmyung Kim, James Liu, Wenhua Liang, Jianxing He, Shideng Bao
Summary: Brain metastasis of lung cancer remains unclear, but this study found that vascular pericytes derived from CD44+ lung cancer stem cells enhance trans-endothelial migration through GPR124, promoting the brain metastasis of lung adenocarcinoma. These cells can survive in circulation and further develop into tumor cells to form metastatic lesions.
Meeting Abstract
Oncology
William D. Gwynne, Yujin Suk Suk, Stefan Custers, Nicholas Mikolajewicz, Jeremy K. Chan, Zsolt Zador, Shawn C. Chafe, Kui Zhai, Laura Escudero, Cunjie Zhang, Olga Zaslaver, Chirayu Chokshi, Muhammad Vaseem Shaikh, David Bakhshinyan, Ian Burns, Iqra Chaudhry, Omri Nachmani, Daniel Mobilio, William T. Maich, Patricia Mero, Kevin R. Brown, Andrew T. Quaile, Chitra Venugopal, Jason Moffat, J. Rafael Montenegro-Burke, Sheila K. Singh
Article
Oncology
Brian J. Golbourn, Matthew E. Halbert, Katharine Halligan, Srinidhi Varadharajan, Brian Krug, Nneka E. Mbah, Nisha Kabir, Ann-Catherine J. Stanton, Abigail L. Locke, Stephanie M. Casillo, Yanhua Zhao, Lauren M. Sanders, Allison Cheney, Steven J. Mullett, Apeng Chen, Michelle Wassell, Anthony Andren, Jennifer Perez, Esther P. Jane, Daniel R. David Premkumar, Robert F. Koncar, Shideh Mirhadi, Lauren H. McCarl, Yue-Fang Chang, Yijen L. Wu, Taylor A. Gatesman, Andrea F. Cruz, Michal Zapotocky, Baoli Hu, Gary Kohanbash, Xiuxing Wang, Alenoush Vartanian, Michael F. Moran, Frank Lieberman, Nduka M. Amankulor, Stacy G. Wendell, Olena M. Vaske, Ashok Panigrahy, James Felker, Kelsey C. Bertrand, Claudia L. Kleinman, Jeremy N. Rich, Robert M. Friedlander, Alberto Broniscer, Costas Lyssiotis, Nada Jabado, Ian F. Pollack, Stephen C. Mack, Sameer Agnihotri
Summary: Agnihotri and colleagues demonstrate that the loss of the MAT2A enzyme in the methionine cycle leads to a depletion of H3K36me3 and increases survival in glioma models. They identify MAT2A as a critical vulnerability in H3K27M gliomas through an RNA screen and show that the depletion of MAT2A reduces H3K36me3 levels, impacting oncogenic and developmental transcription programs. Methionine-restricted diets also extend survival in DMG models.
