title: The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses.
abstract: Infiltration of specialized immune cells regulates the growth and survival of neoplasia. Here, in a survey of public whole genome expression datasets we found that the gene for chemerin, a widely expressed endogenous chemoattractant protein, is down-regulated in melanoma as well as other human tumors. Moreover, high chemerin messenger RNA expression in tumors correlated with improved outcome in human melanoma. In experiments using the B16 transplantable mouse melanoma, tumor-expressed chemerin inhibited in vivo tumor growth without altering in vitro proliferation. Growth inhibition was associated with an altered profile of tumor-infiltrating cells with an increase in natural killer (NK) cells and a relative reduction in myeloid-derived suppressor cells and putative immune inhibitory plasmacytoid dendritic cells. Tumor inhibition required host expression of CMKLR1 (chemokine-like receptor 1), the chemoattractant receptor for chemerin, and was abrogated by NK cell depletion. Intratumoral injection of chemerin also inhibited tumor growth, suggesting the potential for therapeutic application. These results show that chemerin, whether expressed by tumor cells or within the tumor environment, can recruit host immune defenses that inhibit tumorigenesis and suggest that down-regulation of chemerin may be an important mechanism of tumor immune evasion.
authors: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. rkpachynski@stanford.edu
authors: Russell K
authors: RK
authors: Pachynski
authors: Brian A
authors: BA
authors: Zabel
authors: Holbrook E
authors: HE
authors: Kohrt
authors: Nicole M
authors: NM
authors: Tejeda
authors: Justin
authors: J
authors: Monnier
authors: Christina D
authors: CD
authors: Swanson
authors: Alison K
authors: AK
authors: Holzer
authors: Andrew J
authors: AJ
authors: Gentles
authors: Gizette V
authors: GV
authors: Sperinde
authors: Abdolhossein
authors: A
authors: Edalati
authors: Husein A
authors: HA
authors: Hadeiba
authors: Ash A
authors: AA
authors: Alizadeh
authors: Eugene C
authors: EC
authors: Butcher
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002630:Chemotactic Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C102741:CMKLR1 protein, human; C486456:CMKLR1 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse