Cell
Volume 175, Issue 4, 1 November 2018, Pages 1014-1030.e19
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Article
High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy

https://doi.org/10.1016/j.cell.2018.09.030Get rights and content
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Highlights

  • High-dimensional analyses of successful ICT in tumor-bearing mice

  • ICT induces changes in intratumoral myeloid and lymphoid cells

  • Tumor-associated monocytes/macrophages display complex cytokine-driven phenotypes

  • Different cytokines act on tumor-infiltrating monocytes to drive macrophage polarization

Summary

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 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.

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