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
Xianzhe Zhou, Guishan Jin, Junwen Zhang, Fusheng Liu
Summary: As an important part of the glioma immune microenvironment, glioma-associated macrophages (GAMs) play crucial roles in tumor cell resistance to chemotherapy and radiotherapy as well as glioma pathogenesis. Research on GAM polarization and mechanisms of recruitment in the tumor microenvironment has been increasing. Suppressing GAMs at their source is likely to yield better therapeutic outcomes. This article summarizes the origin and recruitment mechanism of GAMs, as well as the therapeutic implications of inhibiting GAMs, aiming to facilitate future glioma-related research and the development of more effective treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Yunzhou Pu, Qing Ji
Summary: This review summarizes the roles and mechanisms of tumor-associated macrophages (TAMs) in the resistance of PD-1/PD-L1 inhibitors. Various therapies, including inhibition of TAM differentiation and re-education of TAM activation, are available to recover the anticancer efficacy of PD-1/PD-L1 inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Chemical
Jen-Tsung Yang, I-Neng Lee, Chun-Han Chen, Fung-Jou Lu, Chiu-Yen Chung, Ming-Hsueh Lee, Yu-Ching Cheng, Kuo-Tai Chen, Jyun-Yu Peng, Ching-Hsein Chen
Summary: Gallic acid can enhance the anti-cancer effect of TMZ by inhibiting Bcl-2 expression and Akt activation, and activating the p38 MAPK pathway. This study provides a potential new approach for the medical treatment of malignant gliomas.
Article
Biochemistry & Molecular Biology
Przemyslaw Wielgat, Natalia Wawrusiewicz-Kurylonek, Robert Czarnomysy, Karol Rogowski, Krzysztof Bielawski, Halina Car
Summary: Paired Siglecs play a role in immune homeostasis and potentially pathogenesis. Dexamethasone and temozolomide may modulate immune responses in gliomas, affecting their therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nanoscience & Nanotechnology
Gilbert Aaron Lee, Wan-Li Lin, Duen-Pang Kuo, Yi-Tien Li, Yu-Wei Chang, Yung-Chie Chen, Shiu-Wen Huang, Justin Bo-Kai Hsu, Cheng-Yu Chen
Summary: Lipid-coated SPIO nanoparticles conjugated with PD-L1 antibodies can specifically target PD-L1 expression in glioblastoma, including temozolomide-resistant cases, as demonstrated in this study through characterizations such as dynamic light scattering and in vivo T2* map MRI analysis. This approach shows promise for early diagnosis and predicting responses to targeted PD-L1 immunotherapy in glioblastoma patients.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Immunology
Xin He, Yuduo Guo, Chunjiang Yu, Hongwei Zhang, Shengdian Wang
Summary: Microglia/macrophages, as the major tumor-infiltrating cells, have been found to promote the malignant progression of gliomas through various pathways. This study evaluated the content of microglia/macrophages in glioma tissues and confirmed their significant relationship with the malignant phenotype of glioma. Epithelial-Mesenchymal Transition (EMT) was identified as the most relevant mechanism of malignant progression to microglia/macrophages. Clinical samples and in vitro co-culture models further demonstrated the promotion of EMT process in glioma cells by microglia/macrophages.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Hao Zhang, Lin Liu, Jinbo Liu, Pengyuan Dang, Shengyun Hu, Weitang Yuan, Zhenqiang Sun, Yang Liu, Chengzeng Wang
Summary: In recent years, tumor immunotherapy, especially immune checkpoint inhibitors, has shown significant progress. However, these treatments are only effective for a small proportion of patients with solid cancers. Tumor-associated macrophages play a crucial role in the tumor microenvironment and have been shown to impact the therapeutic effect of PD-1/PD-L1 inhibitors.
Article
Chemistry, Multidisciplinary
Tao Wang, Yunxia Zhou, Yunping Fan, Hao Duan, Xiaoyu Guo, Jinlong Chang, Youheng Jiang, Changxue Li, Zhang Fu, Yunfei Gao, Xiaoran Guo, Kastytis Sidlauskas, Zhenqiang He, Clive Da Costa, Xia Sheng, Dinglan Wu, Jinqiu Yuan, Huiliang Li, Yulong He, Yonggao Mou, Ningning Li
Summary: This study demonstrates that IDH mutation induces metabolic reprogramming in gliomas and influences the phenotypes of glioma-associated microglia/macrophages (GAMs). Gliomas expressing mutant IDH promote M1-like polarization of GAMs, while typical IDH induces M2-like polarization. Furthermore, the study reveals the involvement of the PERK/miR-19a/LDLR signaling pathway in regulating gliomal cholesterol transport and GAM phenotypes, suggesting it as a potential target pathway for glioma therapy.
Article
Oncology
Yuanfan Yang, Michael C. Brown, Gao Zhang, Kevin Stevenson, Malte Mohme, Reb Kornahrens, Darell D. Bigner, David M. Ashley, Giselle Y. Lopez, Matthias Gromeier
Summary: In malignant gliomas, GAMM contribute to immune suppression and tumor progression through CD155 upregulation. Treatment with PVSRIPO activates GAMM and leads to tumor regression without directly infecting malignant cells. Combination therapy of PVSRIPO and PD1/PD-L1 blockade results in durable remissions.
Article
Multidisciplinary Sciences
Reza Mirzaei, Ashley Gordon, Franz J. Zemp, Mehul Kumar, Susobhan Sarkar, H. Artee Luchman, Anita C. Bellail, Chunhai Hao, Douglas J. Mahoney, Jeff F. Dunn, Pinaki Bose, V. Wee Yong
Summary: The study identified a population of cells coexpressing PD-1 and BTIC marker within the human glioblastoma microenvironment, with tumor-intrinsic PD-1 promoting proliferation and self-renewal of BTICs independently of PD-L1. Additionally, BTIC-intrinsic PD-1 accelerated intracranial tumor growth in mice lacking T and B cells, indicating a nonimmune resistance mechanism to PD-1 or PD-L1-blocking therapies in patients with glioblastoma.
Article
Biochemistry & Molecular Biology
Huan Yu, Huimin Zhong, Na Li, Kaizhe Chen, Junjue Chen, Jun Sun, Lili Xu, Jing Wang, Mingui Zhang, Xiaohong Liu, Lianfu Deng, Ping Huang, Shouyue Huang, Xi Shen, Yisheng Zhong
Summary: The study found that in glaucoma, OPN promotes the proliferation and activation of retinal microglia, leading to glaucomatous optic neuropathy and eventual loss of RGCs and impairment of vision function.This effect may be mediated through the regulation of the p38 MAPK signaling pathway.
Article
Immunology
Ruijie Dong, Zhenyi Xue, Guangyue Fan, Na Zhang, Chengzhi Wang, Guangliang Li, Yurong Da
Summary: Pin1 regulates NLRP3 inflammasome activation through the p38 MAPK signaling pathway in mice, impacting shock mortality and organ damage. Lack of Pin1 reduces NLRP3 inflammasome activation and secretion of inflammatory cytokines, suggesting Pin1 as a potential target for treating inflammatory diseases such as septic shock.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Markus Zeisbrich, Nina Chevalier, Bettina Sehnert, Marta Rizzi, Nils Venhoff, Jens Thiel, Reinhard E. Voll
Summary: This study reveals a deficiency of the immunoinhibitory checkpoint PD-L1 in monocytes from AAV patients. Reduced expression of CMTM6 leads to increased lysosomal degradation of PD-L1, providing insufficient negative signaling to T cells. Correcting this defect by targeting lysosomal function may offer a novel strategy for treating AAV.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Markus P. Kummer, Christina Ising, Christiane Kummer, Heela Sarlus, Angelika Griep, Ana Vieira-Saecker, Stephanie Schwartz, Annett Halle, Matthias Bruckner, Kristian Handler, Joachim L. Schultze, Marc Beyer, Eicke Latz, Michael T. Heneka
Summary: Research indicates that upregulated expression of PD-L1 and PD-1 is found around amyloid plaques in Alzheimer's disease patients and mouse models. Deletion of microglial PD-1 leads to inflammatory responses and impairs Aβ uptake, contributing to increased deposition of Aβ plaques. This highlights the role of ineffective immune regulation by the PD-1/PD-L1 axis in chronic neuroinflammation associated with Alzheimer's disease.
Article
Multidisciplinary Sciences
Jiahui Xu, Xiaoli Yang, Qiaodan Deng, Cong Yang, Dong Wang, Guojuan Jiang, Xiaohong Yao, Xueyan He, Jiajun Ding, Jiankun Qiang, Juchuanli Tu, Rui Zhang, Qun-Ying Lei, Zhi-min Shao, Xiuwu Bian, Ronggui Hu, Lixing Zhang, Suling Liu
Summary: Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). We identified TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously. TEM8 promotes stemness and VM differentiation capacity through a RhoC/ROCK1/SMAD5 axis.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Yun Tan, Wei Zhang, Zhaoqin Zhu, Niu Qiao, Yun Ling, Mingquan Guo, Tong Yin, Hai Fang, Xiaoguang Xu, Gang Lu, Peipei Zhang, Shuangshuang Yang, Ziyu Fu, Dongguo Liang, Yinyin Xie, Ruihong Zhang, Lu Jiang, Shuting Yu, Jing Lu, Fangying Jiang, Jian Chen, Chenlu Xiao, Shengyue Wang, Shuo Chen, Xiu-Wu Bian, Hongzhou Lu, Feng Liu, Saijuan Chen
Summary: The study analyzed clinical laboratory tests, proteomes, and transcriptomes of 963 patients to understand the host responses in COVID-19 progression. Hypercortisolemia was identified as a probable cause of acute lymphocytopenia, while lung cells were found to be potential sources of elevated cytokines mediating systemic immune responses and organ damages. The study provides insights into developing further diagnostics and therapy for COVID-19.
Article
Medicine, Research & Experimental
Min Luo, Yu-Qi Liu, Hua Zhang, Chun-Hua Luo, Qing Liu, Wen-Ying Wang, Zhi-Cheng He, Cong Chen, Xiao-Ning Zhang, Min Mao, Kai-Di Yang, Chao Wang, Xiao-Qing Chen, Wen-Juan Fu, Qin Niu, Xiu-Wu Bian, Yu Shi, Yi-Fang Ping
Summary: The study demonstrates that CPT1A plays a critical role in regulating mitochondrial dynamics and GSC differentiation in glioblastoma. Overexpression of CPT1A inhibits GSC self-renewal and promotes mitochondrial fusion, while disruption of CPT1A leads to mitochondrial fission and reprogramming of non-stem tumor cells towards GSC features. This suggests that CPT1A could be a potential target for differentiation therapy in GBM.
LABORATORY INVESTIGATION
(2022)
Article
Oncology
Kaidi Yang, Yu Shi, Min Luo, Min Mao, Xiaoning Zhang, Cong Chen, Yuqi Liu, Zhicheng He, Qing Liu, Wenying Wang, Chunhua Luo, Wen Yin, Chao Wang, Qin Niu, Hui Zeng, Xiu-Wu Bian, Yi-Fang Ping
Summary: This study used single-cell RNA sequencing and bulk RNA sequencing data to reveal the immune evasion mechanisms of GBM cells and their interactions with immune cells. A new subset of GBM cells, TC-6, was identified with immune-invading characteristics and synergy with tumor-associated macrophages to create an immune-suppressive environment. Three immune subtypes were also identified, with C3 GBMs being enriched with TC-6 cells and immunosuppressive macrophages, which were associated with reduced efficacy of anti-PD-1 treatment. The findings provide new insights into optimizing anti-GBM immunotherapy.
Article
Biochemistry & Molecular Biology
Yu-Qi Liu, Min Luo, Yu Shi, Ying Guo, Hua Zhang, Kai-Di Yang, Tian-Ran Li, Liu-Qing Yang, Ting-Ting Liu, Bo Huang, Qing Liu, Zhi-Cheng He, Xiao-Ning Zhang, Wen-Ying Wang, Shuai Wang, Hui Zeng, Qin Niu, Xia Zhang, You-Hong Cui, Zhi-Ren Zhang, Xiu-Wu Bian, Yi-Fang Ping
Summary: This study found that the genetic deletion of miRNA-processing enzyme Dicer in macrophages can inhibit the growth of glioblastoma and prolong the survival of tumor-bearing mice. The deletion of Dicer in macrophages can change their phenotype, promoting a proinflammatory activation state with enhanced phagocytosis and interferon production, thus improving the ability to eliminate tumor cells.
Article
Chemistry, Multidisciplinary
Li-Hong Wang, Ye Yuan, Jiao Wang, Ying Luo, Yang Lan, Jia Ge, Lei Li, Feng Liu, Qing Deng, Ze-Xuan Yan, Mei Liang, Sen Wei, Xin-Dong Liu, Yan Wang, Yi-Fang Ping, Yu Shi, Shi-Cang Yu, Xia Zhang, You-Hong Cui, Xiao-Hong Yao, Hua Feng, Tao Luo, Xiu-Wu Bian
Summary: A new ASCL2-ATG9B signaling axis crucial for maintaining the stemness phenotype and tumor progression in adult diffuse gliomas is identified, revealing a potential autophagy inhibition strategy.
Article
Oncology
Ye Yuan, Li-Hong Wang, Xian-Xian Zhao, Jiao Wang, Meng-Si Zhang, Qing-Hua Ma, Sen Wei, Ze-Xuan Yan, Yue Cheng, Xiao-Qing Chen, Hong-Bo Zou, Jia Ge, Yan Wang, Xia Zhang, You-Hong Cui, Tao Luo, Xiu-Wu Bian
Summary: This study identified the E3 ubiquitin ligase HUWE1 as a key factor in suppressing GBM progression through the N-Myc-DLL1-NOTCH1 signaling axis. Using the rAAV dual-vector system to deliver dCas9-HUWE1 showed promising antitumor activity in glioma orthotopic xenografts.
CANCER COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Hong Wu, Hongyan Li, Yiqiang Liu, Jingchen Liang, Qianshi Liu, Zhigang Xu, Zhongzhu Chen, Xia Zhang, Kun Zhang, Chuan Xu
Summary: Nanobiotechnology-engineered autologous tumor vaccines (ATVs) camouflaged by tumor cell membrane (TCM) were designed to activate and facilitate the infiltration of cytotoxic T lymphocytes (CTLs) for killing lung tumor cells. PDE5 and PD-L1 dual-target co-inhibition was proposed to unfreeze the immuno-suppressive microenvironment of NSCLC. Studies showed that ATVs with PDE5 inhibitor and NO donor exerted robust anti-tumor effects by increasing iNOS expression, blocking PDE5 pathway, and activating immune responses, resulting in eradication of lung cancers in various models.
BIOACTIVE MATERIALS
(2022)
Article
Oncology
Haofei Liu, Qiwen Zhao, Leyong Tan, Xin Wu, Rui Huang, Yonglin Zuo, Longjuan Chen, Jigui Yang, Zuo-Xin Zhang, Wenchen Ruan, Jiayang Wu, Fei He, Yiliang Fang, Fangyuan Mao, Peipei Zhang, Xiaoning Zhang, Peidi Yin, Zexuan Yan, Wenwen Xu, Huimin Lu, Qingrui Li, Mei Liang, Yanjun Jia, Cong Chen, Senlin Xu, Yu Shi, Yi-Fang Ping, Guang-Jie Duan, Xiao-Hong Yao, Zhijian Han, Tao Pang, Youhong Cui, Xia Zhang, Bo Zhu, Chunjian Qi, Yan Wang, Sheng-Qing Lv, Xiu-Wu Bian, Xindong Liu
Summary: By examining the microenvironment in glioma, we find that tumor-infiltrating T cells are mainly located in the perivascular cuffs and express high levels of CCR5, CXCR3, and PD-1. Analysis of T cell clustering and TCR clone expansion reveals that potential tumor-killing T cells belong to pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. In addition, a distinctive subpopulation of CD4+ T cells with innate-like features and preferential interleukin-8 (IL-8) expression is identified. We demonstrate that IL-8, along with myeloid and tumor cells, coordinates myeloid-derived suppressor cell infiltration and angiogenesis, leading to enhanced tumor growth but reduced efficacy of immune checkpoint blockade therapy. Blockade of IL-8 or its receptor CXCR1/2 unleashes the antitumor immunity mediated by anti-PD-1. Therefore, IL-8 is highlighted as a potential immunotherapy target for glioma.
Article
Cell Biology
Li-Hong Wang, Sen Wei, Ye Yuan, Ming-Jun Zhong, Jiao Wang, Ze-Xuan Yan, Kai Zhou, Tao Luo, Li Liang, Xiu-Wu Bian
Summary: PARP inhibitors have limited efficacy when used alone in glioblastoma (GBM) patients, leading researchers to explore combination therapies. This study found that concurrent treatment with the PARP inhibitor olaparib and XPO1 inhibitor KPT330 showed synergistic anticancer effects on GBM cells. Mechanistically, KPT330 induced the nuclear retention of SQSTM1 and inhibited the ubiquitination of the DNA repair signal H2AX mediated by olaparib in the nucleus, inhibiting DNA damage response and repair in GBM. In the cytoplasm, KPT330 blocked autophagic flux and induced dysfunction of lysosomes, ultimately promoting cell death.
Article
Oncology
Juan Feng, Yang Lan, Feng Liu, Ye Yuan, Jia Ge, Sen Wei, Hu Luo, Jianjun Li, Tao Luo, Xiuwu Bian
Summary: The genomic instability/homologous recombination deficiency (GI/HRD) score has prognostic value in lung adenocarcinoma, particularly when combined with TP53 status, but is not applicable for all types of lung cancer.
NPJ PRECISION ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yan-Xia Wang, Haibo Wu, Yong Ren, Shengqing Lv, Chengdong Ji, Dongfang Xiang, Mengsi Zhang, Huimin Lu, Wenjuan Fu, Qing Liu, Zexuan Yan, Qinghua Ma, Jingya Miao, Ruili Cai, Xi Lan, Bin Wu, Wenying Wang, Yinhua Liu, Dai-Zhong Wang, Mianfu Cao, Zhicheng He, Yu Shi, Yifang Ping, Xiaohong Yao, Xia Zhang, Peng Zhang, Ji Ming Wang, Yan Wang, Youhong Cui, Xiu-Wu Bian
Summary: This study found that Kir2.1 is highly expressed in non-WNT/SHH medulloblastoma and promotes tumor invasion and metastasis by activating the Notch2 signaling pathway. Patients with the Kir2.1(high)/nuclear N2ICD(high) subtype have a significantly shorter lifespan, suggesting it can be used as a biomarker for non-WNT/SHH medulloblastoma.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Qu-Jing Gai, Zhen Fu, Jiang He, Min Mao, Xiao-Xue Yao, Yan Qin, Xi Lan, Lin Zhang, Jing-Ya Miao, Yan-Xia Wang, Jiang Zhu, Fei-Cheng Yang, Hui-Min Lu, Ze-Xuan Yan, Fang-Lin Chen, Yu Shi, Yi-Fang Ping, You-Hong Cui, Xia Zhang, Xindong Liu, Xiao-Hong Yao, Sheng-Qing Lv, Xiu-Wu Bian, Yan Wang
Summary: PDGFRA may not be necessary for PDGFA function. The study revealed EPHA2 as a potential receptor of PDGFA and identified that co-upregulation of PDGFA and EPHA2 led to worse patient prognosis and poorer therapeutic effects. Combination inhibitors targeting PDGFRA and EHA2 represent a promising therapeutic strategy for GBM treatment.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Mingliang Chen, Xunhu Dong, Haoyue Deng, Feng Ye, Yuanpeng Zhao, Jin Cheng, Guorong Dan, Jiqing Zhao, Yan Sai, Xiuwu Bian, Zhongmin Zou
Summary: Nitrogen mustard causes severe vesicating skin injury, partially through over-activating autophagy, and partly by activating the TRPV1-Ca2+-CaMKK beta-AMPK-ULK1 signaling pathway. These results suggest that blocking TRPV1-dependent autophagy could be a potential treatment strategy for nitrogen mustard-caused cutaneous injury.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
