High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy

被引：271

作者：

Gubin, Matthew M. ^{[1
,2
]}

Esaulova, Ekaterina ^{[1
,3
]}

Ward, Jeffrey P. ^{[1
,2
,4
]}

Malkova, Olga N. ^{[2
]}

Runci, Daniele ^{[1
,2
]}

Wong, Pamela ^{[1
]}

Noguchi, Takuro ^{[5
]}

Arthur, Cora D. ^{[1
,2
]}

Meng, Wei ^{[1
,2
]}

Alspach, Elise ^{[1
,2
]}

Medrano, Ruan F. V. ^{[1
,2
]}

Fronick, Catrina ^{[6
]}

Fehlings, Michael ^{[7
]}

Newell, Evan W. ^{[7
]}

Fulton, Robert S. ^{[6
]}

Sheehan, Kathleen C. F. ^{[1
,2
]}

Oh, Stephen T. ^{[2
,8
]}

Schreiber, Robert D. ^{[1
,2
]}

Artyomov, Maxim N. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, St Louis, MO 63130 USA

[3] ITMO Univ, Comp Technol Dept, St Petersburg 197110, Russia

[4] Washington Univ, Sch Med, Dept Med, Div Oncol, 660 South Euclid Ave, St Louis, MO 63110 USA

[5] Shinshu Univ, Sch Med, Dept Comprehens Canc Therapy, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan

[6] Washington Univ, Sch Med, McDonnell Genome Inst, 4444 Forest Pk Ave, St Louis, MO 63108 USA

[7] ASTAR, Singapore Immunol Network SIgN, 8 A Biomed Grove, Singapore 138648, Singapore

[8] Washington Univ, Sch Med, Div Hematol, 660 S Euclid Ave,Campus Box 8125, St Louis, MO 63110 USA

来源：

CELL | 2018年 / 175卷 / 04期

基金：

美国国家卫生研究院;

关键词：

REGULATORY T-CELLS; GENE-EXPRESSION; SINGLE CELLS; IFN-GAMMA; TUMOR; ANTI-CTLA-4; ACTIVATION; BLOCKADE; REVEALS; IMMUNOTHERAPY;

D O I：

10.1016/j.cell.2018.09.030

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：

Although 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 IFN gamma. 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.

引用

页码：1014 / +

页数：36

共 31 条

[1] viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia [J].