Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma

Liu, Haofei; Zhao, Qi-Wen; Tan, Leyong; Wu, Xin; Huang, Rui; Zuo, Yonglin; Chen, Longjuan; Yang, Ji-gui; Zhang, Zuo-Xin; Ruan, Wenchen; Wu, Jiayang; He, Fei; Fang, Yiliang; Mao, Fang‐Yuan; Zhang, Peipei; Zhang, Xiaoning; Yin, Peidi; Yan, Zexuan; Xu, Wenwen; Lu, Huimin; Li, Qingrui; Liang, Mei; Jia, Yushan; Chen, Cong; Xu, Senlin; Shi, Yu; Ping, Yi‐Fang; Duan, Guangjie; Yao, Xiaohong; Han, Ze‐Guang; Pang, Tao; Cui, You‐Hong; Zhang, Xia; Zhu, Bo; Qi, Chunjian; Wang, Yan; Lv, Sheng‐Qing; Bian, Xiu‐Wu; Liu, Xindong

doi:10.1016/j.ccell.2023.03.004

Cited by 51 publications

(23 citation statements)

References 60 publications

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“…Glioma‐associated macrophages and microglia were key elements of glioma TME, regulating tumor growth, invasion, and recurrence (Lin et al., 2023). T cells infiltrated by glioma microenvironment were mainly confined to perivascular areas and expressed high levels of CCR5, CXCR3, and PD‐1 (Liu et al., 2023). Cross‐talk between glioma stem cells and tumor‐associated microglia/macrophages affected clinical occurrence, growth, and multiple tolerance of glioma chemoradiotherapy (Zhu et al., 2023).…”

Section: Discussionmentioning

confidence: 99%

Molecular prognostic of nine parthanatos death‐related genes in glioma, particularly in COL8A1 identification

Fan,

Li,

Liu

2024

Journal of Neurochemistry

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Post‐operative progression and chemotherapy resistance are the main causes of treatment failure in glioma patients. There is a lack of ideal prediction models for post‐operative glioma patient progression and drug sensitivity. We aimed to develop a prognostic model of parthanatos mRNA biomarkers for glioma outcomes. A total of 11 parthanatos genes were obtained from ParthanatosCluster database. ConsensusClusterPlus and R “Limma” package were used to cluster The Cancer Genome Atlas (TCGA)‐glioma cohort and analyze the differential mRNAs. Univariate Cox regression analysis, random survival forest model, and least absolute shrinkage and selection operator (LASSO) regression analysis were used to determine the nine ParthanatosScore prognostic genes combination. ParthanatosScore was verified by 656 patients and 979 patients in TCGA and CGCA‐LGG/GBM datasets. Differences in genomic mutations, tumor microenvironments, and functional pathways were assessed. Drug response prediction was performed using pRRophetic. Kaplan–Meier survival analysis was analyzed. Finally, COL8A1 was selected to evaluate its potential biological function and drug sensitivity of temozolomide and AZD3759 in glioma cells. ParthanatosScore obtained a combination of nine glioma prognostic genes, including CD58, H19, TNFAIP6, FTLP3, TNFRSF11B, SFRP2, LOXL1, COL8A1, and FABP5P7. In the TCGA‐LGG/GBM dataset, glioma prognosis was poor in high ParthanatosScore. Low‐score glioma patients were sensitive to AZD3759_1915, AZD5582_1617, AZD8186_1918, Dasatinib_1079, and Temozolomide_1375, while high‐score patients were less sensitive to these drugs. Compared with HA cells, COL8A1 was significantly over‐expressed in LN229 and U251 cells. Silencing COL8A1 inhibited the malignant characterization of LN229 and U251 cells. Temozolomide and AZD3759 also promoted parthanatos gene expression in glioma cells. Temozolomide and AZD3759 inhibited COL8A1 expression and cell viability and promoted apoptosis in glioma cells and PGM cells. ParthanatosScore can accurately predict clinical prognosis and drug sensitivity after glioma surgery. Silencing COL8A1 inhibited the malignant characterization. Temozolomide and AZD3759 inhibited COL8A1 expression and cell viability and promoted apoptosis and parthanatos gene expression, which is a target to improve glioma.

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Section: Discussionmentioning

confidence: 99%

Molecular prognostic of nine parthanatos death‐related genes in glioma, particularly in COL8A1 identification

Fan,

Li,

Liu

2024

Journal of Neurochemistry

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“…Preclinical studies have suggested that blocking antibody treatments against IL-8 could potentiate greater efficacy of immunotherapies in GBM 77 . While GBM secreted IL-8 has been shown to be an important player driving GBM cancer cell behavior 52 , a major gap in the field remained when it came to understanding how its presence in the TME could be affecting infiltrating macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…In GBM especially, studies have focused on describing the role of IL-8 in promoting glioblastoma stem cells 48 , which are also thought to be major drivers of aggressive GBM tumors, cell migration signaling 75 , and angiogenesis 46,50,76 . Preclinical studies have suggested that blocking antibody treatments against IL-8 could potentiate greater efficacy of immunotherapies in GBM 77 . While GBM secreted IL-8 has been shown to be an important player driving GBM cancer cell behavior 52 , a major gap in the field remained when it came to understanding how its presence in the TME could be affecting infiltrating macrophages.…”

Section: Discussionmentioning

confidence: 99%

IL-8 Instructs Macrophage Identity in Lateral Ventricle Contacting Glioblastoma

Medina,

Brockman,

Cross

et al. 2024

Preprint

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Adult IDH-wildtype glioblastoma (GBM) is a highly aggressive brain tumor with no established immunotherapy or targeted therapy. Recently, CD32+HLA-DRhimacrophages were discovered to have displaced resident microglia in GBM tumors that contact the lateral ventricle stem cell niche. Since these lateral ventricle contacting GBM tumors have especially poor outcomes, identifying the origin and role of these CD32+macrophages is likely critical to developing successful GBM immunotherapies. Here, we identify these CD32+cells as M_IL-8 macrophages and establish that IL-8 is sufficient and necessary for tumor cells to instruct healthy macrophages into CD32+M_IL-8 M2 macrophages. Using a set of 73 GBM tumors, IL-8 protein is shown to be present in GBM tumor cellsin vivoand especially common in tumors contacting the lateral ventricle. Finally, inex vivoexperiments with conditioned medium from primary human tumor cells, inhibitory antibodies to IL-8 blocked the generation of CD32+M_IL-8 cells. These results provide a mechanistic origin for CD32+macrophages that predominate in the microenvironment of the most aggressive GBM tumors. IL-8 and CD32+macrophages should now be explored as targets in combination with GBM immunotherapies, especially for patients whose tumors present with radiographic contact with the ventricular subventricular zone stem cell niche.

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“…Essential for tumor growth and metastasis ( Liu et al, 2023a ; Natale and Bocci, 2023 ), angiogenesis provides TME with necessary nutrients and oxygen, aiding in the growth of cancer cells ( Schaaf et al, 2018 ; Lugano et al, 2020 ; Schito and Rey, 2020 ). TAMs secret factors for promoting angiogenesis, including VEGF ( Schaaf et al, 2018 ), fibroblast growth factors (FGF1 and FGF2) ( Schaaf et al, 2018 ; Im et al, 2020 ), platelet-derived growth factor (PDGF) ( Ntokou et al, 2021 ), hepatocyte growth factor (HGF) ( Choi et al, 2019 ; Dong et al, 2019 ), matrix metalloproteinases (MMP-9, MMP-2) ( Diwanji and Bergmann, 2020 ; Tian et al, 2022 ), and cytokines like IL-8 and IL-1 ( Liu et al, 2023b ; Yang et al, 2023b ). VEGF is crucial for tumoural angiogenesis ( Lai et al, 2019 ; Hwang et al, 2020 ).…”

Section: Pro-tumour Effects Of Tammentioning

confidence: 99%

Tumour-associated macrophages: versatile players in the tumour microenvironment

Ji,

Chan,

Chan

et al. 2023

Front. Cell Dev. Biol.

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Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the classic M1/M2 phenotypes, a number of novel dedifferentiation phenomena of TAMs are discovered due to the advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) and macrophage-neuron transition (MNT). More importantly, emerging information demonstrated the potential of TAMs on cancer immunotherapy, suggesting by the therapeutic efficiency of the checkpoint inhibitors and chimeric antigen receptor engineered cells based on macrophages. Here, we summarized the latest discoveries of TAMs from basic and translational research and discussed their clinical relevance and therapeutic potential for solid cancers.

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Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma

Cited by 51 publications

References 60 publications

Molecular prognostic of nine parthanatos death‐related genes in glioma, particularly in COL8A1 identification

Molecular prognostic of nine parthanatos death‐related genes in glioma, particularly in COL8A1 identification

IL-8 Instructs Macrophage Identity in Lateral Ventricle Contacting Glioblastoma

Tumour-associated macrophages: versatile players in the tumour microenvironment

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