دورية أكاديمية
Single-cell spatial immune landscapes of primary and metastatic brain tumours.
العنوان: | Single-cell spatial immune landscapes of primary and metastatic brain tumours. |
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المؤلفون: | Karimi E; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Yu MW; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Physiology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Maritan SM; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada., Perus LJM; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Physiology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Rezanejad M; Departments of Psychology and Computer Science, University of Toronto, Toronto, Ontario, Canada., Sorin M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Dankner M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada., Fallah P; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada., Doré S; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Zuo D; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Fiset B; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Kloosterman DJ; Division of Tumor Biology and Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands., Ramsay L; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Wei Y; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Lam S; Department of Diagnostic Radiology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Alsajjan R; Department of Medicine, Division of Neurology, King Saud University College of Medicine, Riyadh, Saudi Arabia.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Watson IR; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Roldan Urgoiti G; Department of Oncology, University of Calgary, Calgary, Alberta, Canada.; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada., Park M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Brandsma D; Department of Neuro-Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands., Senger DL; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada., Chan JA; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada., Akkari L; Division of Tumor Biology and Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands., Petrecca K; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute-Hospital, McGill University Health Centre, Montreal, Quebec, Canada., Guiot MC; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute-Hospital, McGill University Health Centre, Montreal, Quebec, Canada.; Department of Pathology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Siegel PM; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada. peter.siegel@mcgill.ca.; Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. peter.siegel@mcgill.ca.; Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. peter.siegel@mcgill.ca.; Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. peter.siegel@mcgill.ca., Quail DF; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada. daniela.quail@mcgill.ca.; Department of Physiology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. daniela.quail@mcgill.ca.; Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. daniela.quail@mcgill.ca., Walsh LA; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada. logan.walsh@mcgill.ca.; Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. logan.walsh@mcgill.ca. |
المصدر: | Nature [Nature] 2023 Feb; Vol. 614 (7948), pp. 555-563. Date of Electronic Publication: 2023 Feb 01. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
مواضيع طبية MeSH: | Brain Neoplasms*/immunology , Brain Neoplasms*/pathology , Brain Neoplasms*/secondary , Glioma*/immunology , Glioma*/pathology , Tumor Microenvironment*/immunology , Single-Cell Analysis*, Humans ; Brain/immunology ; Brain/pathology ; Glioblastoma/immunology ; Glioblastoma/pathology ; Macrophages/enzymology ; Neoplasm Metastasis ; Datasets as Topic |
مستخلص: | Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment 1,2 , yet many single-cell studies lack spatial context and rely on dissociated tissues 3 . Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer. (© 2023. The Author(s).) |
التعليقات: | Comment in: Nat Immunol. 2023 Apr;24(4):565-566. (PMID: 36959293) |
References: | Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423–1437 (2013). (PMID: 24202395395470710.1038/nm.3394) Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541–550 (2018). (PMID: 29686425599882210.1038/s41591-018-0014-x) Baslan, T. & Hicks, J. Unravelling biology and shifting paradigms in cancer with single-cell sequencing. Nat. Rev. Cancer 17, 557–569 (2017). (PMID: 2883571910.1038/nrc.2017.58) Ostrom, Q. T. et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro Oncol. 19, v1–v88 (2017). (PMID: 29117289569314210.1093/neuonc/nox158) Barnholtz-Sloan, J. S. et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J. Clin. Oncol. 22, 2865–2872 (2004). (PMID: 1525405410.1200/JCO.2004.12.149) Stupp, R. et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987–996 (2005). (PMID: 1575800910.1056/NEJMoa043330) Cagney, D. N. et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro Oncol. 19, 1511–1521 (2017). (PMID: 28444227573751210.1093/neuonc/nox077) Quail, D. F. & Joyce, J. A. The microenvironmental landscape of brain tumors. Cancer Cell 31, 326–341 (2017). (PMID: 28292436542426310.1016/j.ccell.2017.02.009) Carvajal-Hausdorf, D. E. et al. Multiplexed (18-Plex) measurement of signaling targets and cytotoxic T cells in trastuzumab-treated patients using imaging mass cytometry. Clin. Cancer Res. 25, 3054–3062 (2019). (PMID: 30796036652227210.1158/1078-0432.CCR-18-2599) Ali, H. R. et al. Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer. Nat. Cancer 1, 163–175 (2020). (PMID: 3512201310.1038/s43018-020-0026-6) Jackson, H. W. et al. The single-cell pathology landscape of breast cancer. Nature 578, 615–620 (2020). (PMID: 3195998510.1038/s41586-019-1876-x) Keren, L. et al. A structured tumor–immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174, 1373–1387.e1319 (2018). (PMID: 30193111613207210.1016/j.cell.2018.08.039) Schürch, C. M. et al. Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front. Cell 182, 1341–1359 (2020). (PMID: 32763154747952010.1016/j.cell.2020.07.005) Liudahl, S. M. et al. Leukocyte heterogeneity in pancreatic ductal adenocarcinoma: phenotypic and spatial features associated with clinical outcome. Cancer Discov. 11, 2014–2031 (2021). (PMID: 33727309833877510.1158/2159-8290.CD-20-0841) Friebel, E. et al. Single-cell mapping of human brain cancer reveals tumor-specific instruction of tissue-invading leukocytes. Cell 181, 1626–1642.e1620 (2020). (PMID: 3247039710.1016/j.cell.2020.04.055) Klemm, F. et al. Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells. Cell 181, 1643–1660.e1617 (2020). (PMID: 32470396855890410.1016/j.cell.2020.05.007) Schaettler, M. O. et al. Characterization of the genomic and immunologic diversity of malignant brain tumors through multisector analysis. Cancer Discov. 12, 154–171 (2022). (PMID: 3461095010.1158/2159-8290.CD-21-0291) Puchalski, R. B. et al. An anatomic transcriptional atlas of human glioblastoma. Science 360, 660–663 (2018). (PMID: 29748285641406110.1126/science.aaf2666) Muller, S. et al. Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment. Genome Biol. 18, 234 (2017). (PMID: 29262845573890710.1186/s13059-017-1362-4) Ginhoux, F., Schultze, J. L., Murray, P. J., Ochando, J. & Biswas, S. K. New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat. Immunol. 17, 34–40 (2016). (PMID: 2668146010.1038/ni.3324) Komohara, Y., Ohnishi, K., Kuratsu, J. & Takeya, M. Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J. Pathol. 216, 15–24 (2008). (PMID: 1855331510.1002/path.2370) Lu-Emerson, C. et al. Increase in tumor-associated macrophages after antiangiogenic therapy is associated with poor survival among patients with recurrent glioblastoma. Neuro Oncol. 15, 1079–1087 (2013). (PMID: 23828240371416010.1093/neuonc/not082) Louis, D. N. et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 23, 1231–1251 (2021). (PMID: 34185076832801310.1093/neuonc/noab106) Prosniak, M. et al. Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers. Clin. Cancer Res. 19, 3776–3786 (2013). (PMID: 2374107210.1158/1078-0432.CCR-12-1940) Park, J. H. et al. Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors. Nat. Immunol. 22, 336–346 (2021). (PMID: 3357461610.1038/s41590-020-00860-7) Reardon, D. A. et al. Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: the CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 6, 1003–1010 (2020). (PMID: 3243750710.1001/jamaoncol.2020.1024) Tawbi, H. A. et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N. Engl. J. Med. 379, 722–730 (2018). (PMID: 30134131801100110.1056/NEJMoa1805453) Long, G. V. et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 19, 672–681 (2018). (PMID: 2960264610.1016/S1470-2045(18)30139-6) Calabrese, C. et al. A perivascular niche for brain tumor stem cells. Cancer Cell 11, 69–82 (2007). (PMID: 1722279110.1016/j.ccr.2006.11.020) Ghajar, C. M. et al. The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15, 807–817 (2013). (PMID: 23728425382691210.1038/ncb2767) Liu, H. et al. Pro-inflammatory and proliferative microglia drive progression of glioblastoma. Cell Rep. 36, 109718 (2021). (PMID: 3452536110.1016/j.celrep.2021.109718) van Hooren, L. et al. Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma. Nat. Commun. 12, 4127 (2021). (PMID: 34226552825776710.1038/s41467-021-24347-7) Kienast, Y. et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16, 116–122 (2010). (PMID: 2002363410.1038/nm.2072) Valiente, M. et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156, 1002–1016 (2014). (PMID: 24581498398847310.1016/j.cell.2014.01.040) Gi, T. et al. Microvascular proliferation of brain metastases mimics glioblastomas in squash cytology. Cytopathology 28, 228–234 (2017). (PMID: 2799565810.1111/cyt.12405) Vanlandewijck, M. et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554, 475–480 (2018). (PMID: 2944396510.1038/nature25739) Arvanitis, C. D., Ferraro, G. B. & Jain, R. K. The blood–brain barrier and blood–tumour barrier in brain tumours and metastases. Nat. Rev. Cancer 20, 26–41 (2020). (PMID: 3160198810.1038/s41568-019-0205-x) Avraham, H. K. et al. Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain. J. Pathol. 232, 369–381 (2014). (PMID: 2442107610.1002/path.4304) Carbonell, W. S., Ansorge, O., Sibson, N. & Muschel, R. The vascular basement membrane as “soil” in brain metastasis. PLoS ONE 4, e5857 (2009). (PMID: 19516901268967810.1371/journal.pone.0005857) Liebner, S. et al. Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 100, 323–331 (2000). (PMID: 1096580310.1007/s004010000180) Akkari, L. et al. Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance. Sci. Transl. Med. 12, eaaw7843 (2020). (PMID: 3266942410.1126/scitranslmed.aaw7843) Pyonteck, S. M. et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med. 19, 1264–1272 (2013). (PMID: 24056773384072410.1038/nm.3337) Quail, D. F. et al. The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 352, aad3018 (2016). (PMID: 27199435545062910.1126/science.aad3018) Sugiyama, S. et al. Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am. J. Pathol. 158, 879–891 (2001). (PMID: 11238037185034210.1016/S0002-9440(10)64036-9) Amorim, A. et al. IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation. Nat. Immunol. 23, 217–228 (2022). (PMID: 3510234410.1038/s41590-021-01117-7) Reynolds, W. F. et al. Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer’s disease. Exp. Neurol. 155, 31–41 (1999). (PMID: 991870210.1006/exnr.1998.6977) Zilionis, R. et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity 50, 1317–1334.e1310 (2019). (PMID: 30979687662004910.1016/j.immuni.2019.03.009) Yanez, A. et al. Granulocyte–monocyte progenitors and monocyte–dendritic cell progenitors independently produce functionally distinct monocytes. Immunity 47, 890–902.e894 (2017). (PMID: 29166589572680210.1016/j.immuni.2017.10.021) Lagasse, E. & Weissman, I. L. Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid lineage. Blood 79, 1907–1915 (1992). (PMID: 137333010.1182/blood.V79.8.1907.1907) Butowski, N. et al. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study. Neuro Oncol. 18, 557–564 (2016). (PMID: 2644925010.1093/neuonc/nov245) Lee, A. H. et al. Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma. Nat. Commun. 12, 6938 (2021). (PMID: 34836966862655710.1038/s41467-021-26940-2) Ravi, V. M. et al. T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10. Nat. Commun. 13, 925 (2022). (PMID: 35177622885442110.1038/s41467-022-28523-1) Xie, Y. et al. Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing. JCI Insight 6, e150861 (2021). (PMID: 342286478410070) Dankner, M. et al. Invasive growth associated with cold-inducible RNA-binding protein expression drives recurrence of surgically resected brain metastases. Neuro Oncol. 23, 1470–1480 (2021). (PMID: 33433612840885810.1093/neuonc/noab002) Dankner, M. et al. The underlying biology and therapeutic vulnerabilities of leptomeningeal metastases in adult solid cancers. Cancers 13, 732 (2021). (PMID: 33578853791658610.3390/cancers13040732) Karimi, E. et al. Machine learning meets classical computer vision for accurate cell identification. Preprint at BioRxiv, https://doi.org/10.1101/2022.02.27.482183 (2022). Arthur, D. & Vassilvitskii, S. k-means++: The advantages of careful seeding. In Proc. 18th annual ACM-SIAM Symposium on Discrete Algorithms 1027–1035 (Society for Industrial and Applied Mathematics, 2006). Peel, D. M. G. Finite Mixture Models (John & Sons, 2000). Schapiro, D. et al. histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data. Nat. Methods 14, 873–876 (2017). (PMID: 28783155561710710.1038/nmeth.4391) Schurch, C. M. et al. Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front. Cell 182, 1341–1359.e1319 (2020). (PMID: 32763154747952010.1016/j.cell.2020.07.005) Uhlen, M. et al. A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science 366, eaax9198 (2019). (PMID: 3185745110.1126/science.aax9198) Fagerland, M. W. t-tests, non-parametric tests, and large studies-a paradox of statistical practice? BMC Med. Res. Methodol. 12, 78 (2012). (PMID: 22697476344582010.1186/1471-2288-12-78) |
المشرفين على المادة: | EC 1.11.1.7 (MPO protein, human) |
تواريخ الأحداث: | Date Created: 20230201 Date Completed: 20230225 Latest Revision: 20230503 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC9931580 |
DOI: | 10.1038/s41586-022-05680-3 |
PMID: | 36725935 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-4687 |
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DOI: | 10.1038/s41586-022-05680-3 |