A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging.
A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging.
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通过多重离子束成像揭示三阴性乳腺癌中具有结构特征的肿瘤免疫微环境
DOI：
10.1016/j.cell.2018.08.039
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发表时间：
2018-09-06
期刊：
影响因子：
64.5
通讯作者：
Angelo M
中科院分区：
文献类型：
--
作者：
Keren L;Bosse M;Marquez D;Angoshtari R;Jain S;Varma S;Yang SR;Kurian A;Van Valen D;West R;Bendall SC;Angelo M
免疫系统在调节癌症进展中至关重要，但对免疫组成、表型和与肿瘤的相互作用的了解有限。我们使用飞行时间复用离子束成像技术（MIBI-TOF）在亚细胞分辨率下同时定量41例三阴性乳腺癌患者36种蛋白质的原位表达，包括身份、功能和免疫调节。包括基于深度学习的分割在内的多步骤处理揭示了个体间肿瘤免疫群体组成的可变性，这与整体免疫浸润和免疫亚群和检查点表达的丰富共存相协调。空间富集分析显示免疫混合和区隔化肿瘤，以细胞类型和位置特异性的方式表达PD1， PD-L1和IDO。沿肿瘤免疫边界的有序免疫结构与区隔化有关，并与生存有关。这些数据证明了肿瘤免疫微环境的组织结构是由细胞组成、空间排列和调节蛋白表达构成的，并为将多路成像应用于免疫肿瘤学提供了一个框架。
The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to simultaneously quantify in-situ expression of 36 proteins covering identity, function and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and enriched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1 and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology.
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影响因子：
50.5
作者：
Burugu, S.;Gao, D.;Nielsen, T. O.
通讯作者：
Nielsen, T. O.
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
48
作者：
Giesen, Charlotte;Wang, Hao A. O.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
影响因子：
168.9
作者：
Denkert, Carsten;Liedtke, Cornelia;von Minckwitz, Gunter
通讯作者：
von Minckwitz, Gunter
影响因子：
10.9
作者：
Fortis SP;Sofopoulos M;Sotiriadou NN;Haritos C;Vaxevanis CK;Anastasopoulou EA;Janssen N;Arnogiannaki N;Ardavanis A;Pawelec G;Perez SA;Baxevanis CN
通讯作者：
Baxevanis CN