NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control.
Reis E Sousa, C
AffiliationImmunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
MetadataShow full item record
AbstractConventional 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 PGE2for immune evasion and that could be exploited for cancer therapy.
CitationNK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. 2018, 172(5):1022-1037.e14 Cell
- Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10.
- Authors: Bergamaschi C, Pandit H, Nagy BA, Stellas D, Jensen SM, Bear J, Cam M, Valentin A, Fox BA, Felber BK, Pavlakis GN
- Issue date: 2020 May
- Intratumoral Immunotherapy with XCL1 and sFlt3L Encoded in Recombinant Semliki Forest Virus-Derived Vectors Fosters Dendritic Cell-Mediated T-cell Cross-Priming.
- Authors: Sánchez-Paulete AR, Teijeira Á, Quetglas JI, Rodríguez-Ruiz ME, Sánchez-Arráez Á, Labiano S, Etxeberria I, Azpilikueta A, Bolaños E, Ballesteros-Briones MC, Casares N, Quezada SA, Berraondo P, Sancho D, Smerdou C, Melero I
- Issue date: 2018 Dec 1
- Are Conventional Type 1 Dendritic Cells Critical for Protective Antitumor Immunity and How?
- Authors: Cancel JC, Crozat K, Dalod M, Mattiuz R
- Issue date: 2019
- A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments.
- Authors: Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, Nelson AE, Loo K, Kumar R, Rosenblum MD, Alvarado MD, Wolf DM, Bogunovic D, Bhardwaj N, Daud AI, Ha PK, Ryan WR, Pollack JL, Samad B, Asthana S, Chan V, Krummel MF
- Issue date: 2018 Aug
- Natural Killer Cells Recruit Dendritic Cells to Promote Antitumor Immunity.
- Issue date: 2018 Apr