Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

被引：691

作者：

Klemm, Florian ^{[1
,2
]}

Maas, Roeltje R. ^{[1
,2
,3
,4
]}

Bowman, Robert L. ^{[5
]}

Kornete, Mara ^{[1
,2
]}

Soukup, Klara ^{[1
,2
]}

Nassiri, Sina ^{[1
,2
,6
]}

Brouland, Jean-Philippe ^{[7
]}

Iacobuzio-Donahue, Christine A. ^{[8
]}

Brennan, Cameron ^{[9
]}

Tabar, Viviane ^{[9
]}

Gutin, Philip H. ^{[9
]}

Daniel, Roy T. ^{[4
]}

Hegi, Monika E. ^{[3
,4
]}

Joyce, Johanna A. ^{[1
,2
]}

机构：

[1] Univ Lausanne, Dept Oncol, Lausanne, Switzerland

[2] Univ Lausanne, Ludwig Inst Canc Res, Lausanne, Switzerland

[3] CHU Vaudois, Neurosci Res Ctr, Lausanne, Switzerland

[4] CHU Vaudois, Dept Neurosurg, Lausanne, Switzerland

[5] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[6] SIB Swiss Inst Bioinformat, Bioinformat Core Facil, Lausanne, Switzerland

[7] CHU Vaudois, Dept Pathol, Lausanne, Switzerland

[8] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA

[9] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, 1275 York Ave, New York, NY 10021 USA

来源：

CELL | 2020年 / 181卷 / 07期

基金：

奥地利科学基金会;

关键词：

MACROPHAGE POLARIZATION; CANCER PROGRESSION; INHIBITION; RESISTANCE; DATABASE;

D O I：

10.1016/j.cell.2020.05.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease, We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and spatial tissue characterization. This revealed disease-specific enrichment of immune cells with pronounced differences in proportional abundance of tissue-resident microglia, infiltrating monocyte-derived macrophages, neutrophils, and T cells, These integrated analyses also uncovered multifaceted immune cell activation within brain malignancies entailing converging transcriptional trajectories while maintaining disease- and cell-typespecific programs. Given the interest in developing TME-targeted therapies for brain malignancies, this comprehensive resource of the immune landscape offers insights into possible strategies to overcome tumor-supporting TME properties and instead harness the TME to fight cancer.

引用

页码：1643 / +

页数：35

共 95 条

[1] Tumor macrophages are pivotal constructors of tumor collagenous matrix [J].

Afik, Ran ;

Zigmond, Ehud ;

Vugman, Milena ;

Klepfish, Mordehay ;

Shimshoni, Elee ;

Pasmanik-Chor, Metsada ;

Shenoy, Anjana ;

Bassat, Elad ;

Halpern, Zamir ;

Geiger, Tamar ;

Sagi, Irit ;

Varol, Chen .

JOURNAL OF EXPERIMENTAL MEDICINE, 2016, 213 (11) :2315-2331

[2] Challenges to curing primary brain tumours [J].

Aldape, Kenneth ;

Brindle, Kevin M. ;

Chesler, Louis ;

Chopra, Rajesh ;

Gajjar, Amar ;

Gilbert, Mark R. ;

Gottardo, Nicholas ;

Gutmann, David H. ;

Hargrave, Darren ;

Holland, Eric C. ;

Jones, David T. W. ;

Joyce, Johanna A. ;

Kearns, Pamela ;

Kieran, Mark W. ;

Mellinghoff, Ingo K. ;

Merchant, Melinda ;

Pfister, Stefan M. ;

Pollard, Steven M. ;

Ramaswamy, Vijay ;

Rich, Jeremy N. ;

Robinson, Giles W. ;

Rowitch, David H. ;

Sampson, John H. ;

Taylor, Michael D. ;

Workman, Paul ;

Gilbertson, Richard J. .

NATURE REVIEWS CLINICAL ONCOLOGY, 2019, 16 (08) :509-520

[3]

Baddeley A, 2016, CHAP HALL CRC INTERD, P1

[4] Regulation of Neutrophil Function by Adenosine [J].

Barletta, Kathryn E. ;

Ley, Klaus ;

Mehrad, Borna .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2012, 32 (04) :856-864

[5] Fitting Linear Mixed-Effects Models Using lme4 [J].

Bates, Douglas ;

Maechler, Martin ;

Bolker, Benjamin M. ;

Walker, Steven C. .

JOURNAL OF STATISTICAL SOFTWARE, 2015, 67 (01) :1-48

[6] Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade [J].

Benci, Joseph L. ;

Xu, Bihui ;

Qiu, Yu ;

Wu, Tony J. ;

Dada, Hannah ;

Twyman-Saint Victor, Christina ;

Cucolo, Lisa ;

Lee, David S. M. ;

Pauken, Kristen E. ;

Huang, Alexander C. ;

Gangadhar, Tara C. ;

Amaravadi, Ravi K. ;

Schuchter, Lynn M. ;

Feldman, Michael D. ;

Ishwaran, Hemant ;

Vonderheide, Robert H. ;

Maity, Amit ;

Wherry, E. John ;

Minn, Andy J. .

CELL, 2016, 167 (06) :1540-+

[7] Death to the bad guys: Targeting cancer via Apo2L/TRAIL [J].

Bouralexis, S ;

Findlay, DM ;

Evdokiou, A .

APOPTOSIS, 2005, 10 (01) :35-51

[8] The Role and Function of Fcγ Receptors on Myeloid Cells [J].

Bournazos, Stylianos ;

Wang, Taia T. ;

Ravetch, Jeffrey V. .

MICROBIOLOGY SPECTRUM, 2016, 4 (06)

[9] Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies [J].

Bowman, Robert L. ;

Klemm, Florian ;

Akkari, Leila ;

Pyonteck, Stephanie M. ;

Sevenich, Lisa ;

Quail, Daniela F. ;

Dhara, Surajit ;

Simpson, Kenishana ;

Gardner, Eric E. ;

Iacobuzio-Donahue, Christine A. ;

Brennan, Cameron W. ;

Tabar, Viviane ;

Gutin, Philip H. ;

Joyce, Johanna A. .

CELL REPORTS, 2016, 17 (09) :2445-2459

[10] Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study [J].

Cagney, Daniel N. ;

Martin, Allison M. ;

Catalano, Paul J. ;

Redig, Amanda J. ;

Lin, Nancy U. ;

Lee, Eudocia Q. ;

Wen, Patrick Y. ;

Dunn, Ian F. ;

Bi, Wenya Linda ;

Weiss, Stephanie E. ;

Haas-Kogan, Daphne A. ;

Alexander, Brian M. ;

Aizer, Ayal A. .

NEURO-ONCOLOGY, 2017, 19 (11) :1511-1521

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