van den Bent, M. J. et al. Primary brain tumours in adults. Lancet 402, 1564–1579 (2023).
Andersen, B. M. et al. Glial and myeloid heterogeneity in the brain tumour microenvironment. Nat. Rev. Cancer 21, 786–802 (2021).
Clark, I. C. et al. Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science 372, eabf1230 (2021).
Mathewson, N. D. et al. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell 184, 1281–1298.e26 (2021).
Takenaka, M. C. et al. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat. Neurosci. 22, 729–740 (2019).
Kirschenbaum, D. et al. Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma. Cell 187, 149–165 (2024).
Hara, T. et al. Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. Cancer Cell 39, 779–792 (2021).
Friebel, E. et al. Single-cell mapping of human brain cancer reveals tumor-specific instruction of tissue-invading leukocytes. Cell 181, 1626–1642 (2020).
Lee, H.-G., Wheeler, M. A. & Quintana, F. J. Function and therapeutic value of astrocytes in neurological diseases. Nat. Rev. Drug Discov. 21, 339–358 (2022).
Sofroniew, M. V. Astrocyte barriers to neurotoxic inflammation. Nat. Rev. Neurosci. 16, 249–263 (2015).
Couturier, C. P. et al. Glioblastoma scRNA-seq shows treatment-induced, immune-dependent increase in mesenchymal cancer cells and structural variants in distal neural stem cells. Neuro Oncol. 24, 1494–1508 (2022).
Müller, S. et al. Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas. Mol. Syst. Biol. 12, 889 (2016).
Gan, H. K., Kaye, A. H. & Luwor, R. B. The EGFRvIII variant in glioblastoma multiforme. J. Clin. Neurosci. 16, 748–754 (2009).
Keskin, D. B. et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565, 234–239 (2019).
Ravi, V. M. et al. Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. Cancer Cell 40, 639–655 (2022).
Greenwald, A. C. et al. Integrative spatial analysis reveals a multi-layered organization of glioblastoma. Cell 187, 2485–2501 (2024).
Saunders, A. et al. Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries. Nat. Commun. 13, 6993 (2022).
Weinlich, R., Oberst, A., Beere, H. M. & Green, D. R. Necroptosis in development, inflammation and disease. Nat. Rev. Mol. Cell Biol. 18, 127–136 (2017).
Callow, M. G. et al. CRISPR whole-genome screening identifies new necroptosis regulators and RIPK1 alternative splicing. Cell Death Dis. 9, 261 (2018).
Levy, A. et al. CD38 deficiency in the tumor microenvironment attenuates glioma progression and modulates features of tumor-associated microglia/macrophages. Neuro Oncol. 14, 1037–1049 (2012).
Ma, K., Chen, S., Chen, X., Zhao, X. & Yang, J. CD93 is associated with glioma-related malignant processes and immunosuppressive cell infiltration as an inspiring biomarker of survivance. J. Mol. Neurosci. 72, 2106–2124 (2022).
Yang, F., Zhang, X., Wang, X., Xue, Y. & Liu, X. The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma. Front. Genet. 13, 1029270 (2022).
Mu, L. et al. Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme. Front. Immunol. 13, 842524 (2022).
Lu, B. et al. Basic transcription factor 3 like 4 enhances malignant phenotypes through modulating tumor cell function and immune microenvironment in glioma. Am. J. Pathol. 194, 772–784 (2024).
Ma, K., Chen, S., Chen, X., Yang, C. & Yang, J. S100A10 is a new prognostic biomarker related to the malignant molecular features and immunosuppression process of adult gliomas. World Neurosurg. 165, e650–e663 (2022).
Walther, A., Riehemann, K. & Gerke, V. A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Mol. Cell 5, 831–840 (2000).
Puchalski, R. B. et al. An anatomic transcriptional atlas of human glioblastoma. Science 360, 660–663 (2018).
Guo, K. et al. A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing. Front. Mol. Biosci. 9, 984712 (2022).
Sun, L. et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213–227 (2012).
Chesnokov, M., Khan, I. & Chefetz, I. Induction and detection of necroptotic cell death in mammalian cell culture. Methods Mol. Biol. 2255, 119–134 (2021).
Orozco, S. et al. RIPK1 both positively and negatively regulates RIPK3 oligomerization and necroptosis. Cell Death Differ. 21, 1511–1521 (2014).
Iizuka, Y. et al. Identification of a glioma antigen, GARC-1, using cytotoxic T lymphocytes induced by HSV cancer vaccine. Int. J. Cancer 118, 942–949 (2006).
Gerke, V. et al. Annexins—a family of proteins with distinctive tastes for cell signaling and membrane dynamics. Nat. Commun. 15, 1574 (2024).
Franchi, L. et al. Cytosolic double-stranded RNA activates the NLRP3 inflammasome via MAVS-induced membrane permeabilization and K+ efflux. J. Immunol. 193, 4214–4222 (2014).
Li, Z. et al. Formyl peptide receptor 1 signaling potentiates inflammatory brain injury. Sci. Transl. Med. 13, eabe9890 (2021).
Weiß, E. & Kretschmer, D. Formyl-peptide receptors in infection, inflammation, and cancer. Trends Immunol. 39, 815–829 (2018).
Sanmarco, L. M. et al. Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. Nature 590, 473–479 (2021).
Wheeler, M. A. et al. MAFG-driven astrocytes promote CNS inflammation. Nature 578, 593–599 (2020).
Wheeler, M. A. et al. Environmental control of astrocyte pathogenic activities in CNS inflammation. Cell 176, 581–596 (2019).
Wheeler, M. A. et al. Droplet-based forward genetic screening of astrocyte-microglia cross-talk. Science 379, 1023–1030 (2023).
Kiss, M. G. et al. Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis. Immunity 56, 1502–1514 (2023).
Schnell, A. et al. Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity. Cell 184, 6281–6298 (2021).
Meiser, P. et al. A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity. Cancer Cell 41, 1498–1515 (2023).
Bowman-Kirigin, J. A. et al. The conventional dendritic cell 1 subset primes CD8+ T cells and traffics tumor antigen to drive antitumor immunity in the brain. Cancer Immunol. Res. 11, 20–37 (2023).
Maas, R. R. et al. The local microenvironment drives activation of neutrophils in human brain tumors. Cell 186, 4546–4566.e27 (2023).
Priego, N. et al. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat. Med. 24, 1024–1035 (2018).
Heiland, D. H. et al. Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma. Nat. Commun. 10, 2541 (2019).
Pepinsky, R. B. et al. Purification and partial sequence analysis of a 37-kDa protein that inhibits phospholipase A2 activity from rat peritoneal exudates. J. Biol. Chem. 261, 4239–4246 (1986).
Wu, C. C. et al. Lipocortin 1 mediates the inhibition by dexamethasone of the induction by endotoxin of nitric oxide synthase in the rat. Proc. Natl Acad. Sci. USA 92, 3473–3477 (1995).
Ferlazzo, V. et al. Anti-inflammatory effects of annexin-1: stimulation of IL-10 release and inhibition of nitric oxide synthesis. Int. Immunopharmacol. 3, 1363–1369 (2003).
Sanches, J. M. et al. Annexin A1 regulates NLRP3 inflammasome activation and modifies lipid release profile in isolated peritoneal macrophages. Cells 9, 926 (2020).
Chao, C.-C. et al. Metabolic control of astrocyte pathogenic activity via cPLA2-MAVS. Cell 179, 1483–1498 (2019).
Zhou, Y. et al. Formylpeptide receptor FPR and the rapid growth of malignant human gliomas. J. Natl Cancer Inst. 97, 823–835 (2005).
Yatim, N. et al. RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8+ T cells. Science 350, 328–334 (2015).
Han, M. et al. Regulated cell death in glioma: promising targets for natural small-molecule compounds. Front. Oncol. 14, 1273841 (2024).
Sun, W. et al. Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells. Free Radic. Biol. Med. 108, 433–444 (2017).
Nomura, M., Ueno, A., Saga, K., Fukuzawa, M. & Kaneda, Y. Accumulation of cytosolic calcium induces necroptotic cell death in human neuroblastoma. Cancer Res. 74, 1056–1066 (2014).
Venkataramani, V. et al. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 573, 532–538 (2019).
Bagley, S. J. et al. Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results. Nat. Med. 30, 1320–1329 (2024).
Lim, M. et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 24, 1935–1949 (2022).
Lee, Y., Messing, A., Su, M. & Brenner, M. GFAP promoter elements required for region-specific and astrocyte-specific expression. Glia 56, 481–493 (2008).
Hunker, A. C. et al. Conditional single vector CRISPR/SaCas9 viruses for efficient mutagenesis in the adult mouse nervous system. Cell Rep. 30, 4303–4316 (2020).
Challis, R. C. et al. Systemic AAV vectors for widespread and targeted gene delivery in rodents. Nat. Protoc. 14, 379–414 (2019).
Opitz, C. A. et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478, 197–203 (2011).
Gut, G., Herrmann, M. D. & Pelkmans, L. Multiplexed protein maps link subcellular organization to cellular states. Science 361, eaar7042 (2018).
Brennan, C. W. et al. The somatic genomic landscape of glioblastoma. Cell 155, 462–477 (2013).
Barthel, F. P. et al. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 576, 112–120 (2019).
Cerami, E. et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401–404 (2012).
Barbie, D. A. et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462, 108–112 (2009).
Chu, T., Wang, Z., Pe’er, D. & Danko, C. G. Cell type and gene expression deconvolution with BayesPrism enables Bayesian integrative analysis across bulk and single-cell RNA sequencing in oncology. Nat. Cancer 3, 505–517 (2022).
Verhaak, R. G. W. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2010).
Maire, C. L. et al. Glioma escape signature and clonal development under immune pressure. J. Clin. Invest. 130, 5257–5271 (2020).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Müller, S., Cho, A., Liu, S. J., Lim, D. A. & Diaz, A. CONICS integrates scRNA-seq with DNA sequencing to map gene expression to tumor sub-clones. Bioinformatics 34, 3217–3219 (2018).
Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163–172 (2019).
Zorita, E., Cuscó, P. & Filion, G. J. Starcode: sequence clustering based on all-pairs search. Bioinformatics 31, 1913–1919 (2015).
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).
Lun, A. T. L. et al. EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. Genome Biol. 20, 63 (2019).
Griffiths, J. A., Richard, A. C., Bach, K., Lun, A. T. L. & Marioni, J. C. Detection and removal of barcode swapping in single-cell RNA-seq data. Nat. Commun. 9, 2667 (2018).
Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
