Single-cell spatial immune landscapes of primary and metastatic brain tumours

被引:170
作者
Karimi, Elham [1 ]
Yu, Miranda W. W. [1 ,2 ]
Maritan, Sarah M. [1 ,3 ]
Perus, Lucas J. M. [1 ,2 ]
Rezanejad, Morteza [4 ]
Sorin, Mark [1 ,5 ]
Dankner, Matthew [1 ,3 ]
Fallah, Parvaneh [6 ]
Dore, Samuel [1 ,5 ]
Zuo, Dongmei [1 ]
Fiset, Benoit [1 ]
Kloosterman, Daan J. [7 ]
Ramsay, LeeAnn [1 ]
Wei, Yuhong [1 ]
Lam, Stephanie [8 ]
Alsajjan, Roa [9 ,10 ]
Watson, Ian R. [1 ,11 ]
Roldan Urgoiti, Gloria [12 ,13 ]
Park, Morag [1 ,6 ,11 ]
Brandsma, Dieta [14 ]
Senger, Donna L. [6 ,15 ]
Chan, Jennifer A. A. [13 ,16 ]
Akkari, Leila [7 ]
Petrecca, Kevin [10 ,17 ]
Guiot, Marie-Christine [1 ,10 ,17 ,18 ]
Siegel, Peter M. [1 ,3 ,11 ,19 ]
Quail, Daniela F. [1 ,2 ,3 ]
Walsh, Logan A. [1 ,5 ]
机构
[1] McGill Univ, Rosalind & Morris Goodman Canc Inst, Montreal, PQ, Canada
[2] McGill Univ, Fac Med, Dept Physiol, Montreal, PQ, Canada
[3] McGill Univ, Dept Med, Div Expt Med, Montreal, PQ, Canada
[4] Univ Toronto, Dept Psychol & Comp Sci, Toronto, ON, Canada
[5] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ, Canada
[6] McGill Univ, Gerald Bronfman Dept Oncol, Montreal, PQ, Canada
[7] Netherlands Canc Inst, Oncode Inst, Div Tumor Biol & Immunol, Amsterdam, Netherlands
[8] McGill Univ, Fac Med, Dept Diagnost Radiol, Montreal, PQ, Canada
[9] King Saud Univ, Dept Med, Div Neurol, Coll Med, Riyadh, Saudi Arabia
[10] McGill Univ, Fac Med, Dept Neurol & Neurosurg, Montreal, PQ, Canada
[11] McGill Univ, Fac Med, Dept Biochem, Montreal, PQ, Canada
[12] Univ Calgary, Dept Oncol, Calgary, AB, Canada
[13] Univ Calgary, Arnie Charbonneau Canc Inst, Calgary, AB, Canada
[14] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Neurooncol, Amsterdam, Netherlands
[15] Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ, Canada
[16] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada
[17] McGill Univ, Montreal Neurol Inst Hosp, Hlth Ctr, Montreal, PQ, Canada
[18] McGill Univ, Fac Med, Dept Pathol, Montreal, PQ, Canada
[19] McGill Univ, Fac Med, Dept Anat & Cell Biol, Montreal, PQ, Canada
基金
加拿大健康研究院;
关键词
CENTRAL-NERVOUS-SYSTEM; MICROENVIRONMENTAL LANDSCAPE; PERIVASCULAR NICHE; CANCER; REVEALS; GLIOBLASTOMA; CYTOMETRY; SURVIVAL; ATLAS;
D O I
10.1038/s41586-022-05680-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:555 / +
页数:28
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