Cell · 2018

NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis e Sousa C

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Böttcher JP — Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: j.boettcher@tum.de.
Bonavita E — Cancer Inflammation and Immunity Group, CRUK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
Chakravarty P — Bioinformatics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Blees H — Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cabeza-Cabrerizo M — Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Sammicheli S — Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Rogers NC — Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Sahai E — Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Zelenay S — Cancer Inflammation and Immunity Group, CRUK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
Reis e Sousa C — Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: caetano@crick.ac.uk.

Open on PubMed ↗Open at publisher ↗PMID 29429633

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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.