Cell
Volume 172, Issue 5, 22 February 2018, Pages 1022-1037.e14
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Article
NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

https://doi.org/10.1016/j.cell.2018.01.004Get rights and content
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Highlights

  • NK cells recruit cDC1 into the tumor microenvironment

  • cDC1 recruitment depends on NK cell-derived chemokines CCL5 and XCL1

  • The NK cell/chemokine/cDC1 axis is associated with cancer patient survival

  • Tumor-derived PGE2 impairs NK cell and cDC1 resulting in cancer immune evasion

Summary

Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival. Notably, tumor production of prostaglandin E2 (PGE2) leads to evasion of the NK cell-cDC1 axis in part by impairing NK cell viability and chemokine production, as well as by causing downregulation of chemokine receptor expression in cDC1. Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.

Keywords

dendritic cells
tumor microenvironment
tumor immune control
cancer immunotherapy
immune evasion

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Present address: Institute of Molecular Immunology and Experimental Oncology, Klinikum München rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany

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