High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy.
High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy.
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高维分析描述了成功的免疫检查癌症治疗过程中髓样和淋巴室的重塑。
DOI：
10.1016/j.cell.2018.09.030
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发表时间：
2018-11-01
期刊：
影响因子：
64.5
通讯作者：
Artyomov MN
中科院分区：
文献类型：
--
作者：
Gubin MM;Esaulova E;Ward JP;Malkova ON;Runci D;Wong P;Noguchi T;Arthur CD;Meng W;Alspach E;Medrano RFV;Fronick C;Fehlings M;Newell EW;Fulton RS;Sheehan KCF;Oh ST;Schreiber RD;Artyomov MN
虽然目前的免疫检查点疗法（ICT）主要针对淋巴细胞，但它与肿瘤微环境的更广泛重塑有关。在这里，使用互补形式的高维分析，我们定义了在无限制的肿瘤生长或有效的ICT过程中来自同基因小鼠肿瘤的所有造血细胞的差异。通过单细胞RNA测序（scRNAseq）对肿瘤浸润细胞的基因表达的无偏评估和通过质谱细胞术（CyTOF）对细胞蛋白表达的纵向评估揭示了淋巴样和髓样肿瘤内隔室的显著重塑。令人惊讶的是，我们观察到单核细胞/巨噬细胞的多个亚群，可通过标记物CD 206、CX 3CR 1、CD 1d和iNOS进行区分，这些亚群在ICT期间以部分依赖于IFNγ的方式随时间变化。我们的数据支持这样的假设，即这种巨噬细胞极化/活化是由于对循环单核细胞和进入肿瘤的早期巨噬细胞的影响，而不是对预极化的成熟肿瘤内巨噬细胞的影响。概述了成功的免疫检查点治疗期间肿瘤微环境的全面变化，暗示了浸润巨噬细胞在抗肿瘤免疫环境中的极化的关键作用。
While current immune checkpoint therapy (ICT) mainly targets lymphoid cells, it is associated with a broader remodeling of the tumor micro-environment. Here, using complementary forms of high dimensional profiling, we define differences across all hematopoietic cells from syngeneic mouse tumors during unrestrained tumor growth or effective ICT. Unbiased assessment of gene expression of tumor infiltrating cells by single cell RNA sequencing (scRNAseq) and longitudinal assessment of cellular protein expression by mass cytometry (CyTOF) revealed significant remodeling of both the lymphoid and myeloid intratumoral compartments. Surprisingly, we observed multiple subpopulations of monocytes/macrophages, distinguishable by the markers CD206, CX3CR1, CD1d and iNOS, that change over time during ICT in a manner partially dependent on IFNγ. Our data support the hypothesis that this macrophage polarization/activation results from effects on circulatory monocytes and early macrophages entering tumors, rather than on pre-polarized mature intratumoral macrophages. Comprehensive changes in the tumor microenvironment during successful immune checkpoint therapy are profiled, implicating a key role for polarization of infiltrating macrophages in the anti-tumor immune milieu
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影响因子：
64.5
作者：
Levine JH;Simonds EF;Bendall SC;Davis KL;Amir el-AD;Tadmor MD;Litvin O;Fienberg HG;Jager A;Zunder ER;Finck R;Gedman AL;Radtke I;Downing JR;Pe'er D;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.8
作者：
Matsushita, Hirokazu;Vesely, Matthew D.;Koboldt, Daniel C.;Rickert, Charles G.;Uppaluri, Ravindra;Magrini, Vincent J.;Arthur, Cora D.;White, J. Michael;Chen, Yee-Shiuan;Shea, Lauren K.;Hundal, Jasreet;Wendl, Michael C.;Demeter, Ryan;Wylie, Todd;Allison, James P.;Smyth, Mark J.;Old, Lloyd J.;Mardis, Elaine R.;Schreiber, Robert D.
通讯作者：
Schreiber, Robert D.
影响因子：
64.8
作者：
Shankaran, V;Ikeda, H;Schreiber, RD
通讯作者：
Schreiber, RD
DOI：
10.1084/jem.20130579
发表时间：
2013-08-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Simpson TR;Li F;Montalvo-Ortiz W;Sepulveda MA;Bergerhoff K;Arce F;Roddie C;Henry JY;Yagita H;Wolchok JD;Peggs KS;Ravetch JV;Allison JP;Quezada SA
通讯作者：
Quezada SA
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO