Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells.
Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells.
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DOI：
10.1016/j.cell.2020.05.007
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发表时间：
2020-06-25
期刊：
影响因子：
64.5
通讯作者：
Joyce JA
中科院分区：
文献类型：
--
作者：
Klemm F;Maas RR;Bowman RL;Kornete M;Soukup K;Nassiri S;Brouland JP;Iacobuzio-Donahue CA;Brennan C;Tabar V;Gutin PH;Daniel RT;Hegi ME;Joyce JA
脑恶性肿瘤包括一系列原发性和转移性癌症，包括低级别和高级别神经胶质瘤，以及源自各种颅外肿瘤的脑转移瘤（BrM）。我们对脑肿瘤微环境（TME）的了解仍然有限，并且不知道它是否由原发性与转移性疾病差异塑造。因此，我们通过流式细胞术、RNA测序、蛋白质阵列、培养测定和空间组织表征全面分析了脑TME景观。这揭示了免疫细胞的疾病特异性富集，其中组织驻留小胶质细胞、浸润性单核细胞衍生的巨噬细胞、中性粒细胞和T细胞的比例丰度存在显著差异。这些综合分析还揭示了脑恶性肿瘤中多方面的免疫细胞激活，需要收敛转录轨迹，同时保持疾病和细胞类型特异性程序。鉴于对开发脑恶性肿瘤的TME靶向疗法的兴趣，这种免疫景观的综合资源提供了对克服肿瘤支持TME特性的可能策略的见解，而是利用TME来对抗癌症。
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 type-specific 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.
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影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
4.8
作者：
Huang, Qi-Quan;Hossain, M. Moazzem;Jin, Jian-Ping
通讯作者：
Jin, Jian-Ping
影响因子：
3.7
作者：
Bournazos, Stylianos;Wang, Taia T.;Ravetch, Jeffrey V.
通讯作者：
Ravetch, Jeffrey V.
影响因子：
64.5
作者：
Ceccarelli M;Barthel FP;Malta TM;Sabedot TS;Salama SR;Murray BA;Morozova O;Newton Y;Radenbaugh A;Pagnotta SM;Anjum S;Wang J;Manyam G;Zoppoli P;Ling S;Rao AA;Grifford M;Cherniack AD;Zhang H;Poisson L;Carlotti CG Jr;Tirapelli DP;Rao A;Mikkelsen T;Lau CC;Yung WK;Rabadan R;Huse J;Brat DJ;Lehman NL;Barnholtz-Sloan JS;Zheng S;Hess K;Rao G;Meyerson M;Beroukhim R;Cooper L;Akbani R;Wrensch M;Haussler D;Aldape KD;Laird PW;Gutmann DH;TCGA Research Network;Noushmehr H;Iavarone A;Verhaak RG
通讯作者：
Verhaak RG