Chemerin partly mediates tumor‐inhibitory effect of all‐ trans retinoic acid via CMKLR 1‐dependent natural killer cell recruitment

Autor:	Yan Song, Rui He, Yanjun Dan, Wei Yin, Jiangxin Sheng, Yixuan Zeng
Rok vydání:	2019
Předmět:	0301 basic medicine Skin Neoplasms Immunology Melanoma Experimental Retinoic acid Antineoplastic Agents Tretinoin Endogeny CMKLR1 Receptors G-Protein-Coupled Natural killer cell 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immunity Cell Line Tumor Tumor Microenvironment medicine Animals Immunology and Allergy Chemerin neoplasms Cell Proliferation Mice Knockout biology Chemistry Melanoma Cancer Original Articles medicine.disease Tumor Burden Killer Cells Natural Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Cancer research biology.protein Intercellular Signaling Peptides and Proteins Receptors Chemokine Tumor Escape Chemokines 030215 immunology
Zdroj:	Immunology
ISSN:	1365-2567 0019-2805
DOI:	10.1111/imm.13065
Popis:	Down‐regulated chemerin expression has been reported to correlate with poor prognosis of several types of cancer including melanoma. All‐trans retinoic acid (atRA) is a potent inducer of chemerin, and we previously reported that atRA inhibited murine melanoma growth through enhancement of anti‐tumor T‐cell immunity. Here, we aimed to investigate whether loss of endogenous chemerin accelerated melanoma growth and whether chemerin was involved in the melanoma‐inhibitory effect of atRA. We demonstrated that chemerin was constitutively expressed in the skin, which was down‐regulated during murine melanoma growth. Rarres2 (−/−) mice, which are deficient in chemerin, exhibited aggravated tumor growth and impaired tumor‐infiltrating natural killer (NK) cells that express CMKLR1, the functional receptor of chemerin. Topical treatment with atRA up‐regulated skin chemerin expression, which was primarily derived from dermal cells. Moreover, atRA treatment significantly enhanced tumor‐infiltrating NK cells, which was completely abrogated in Rarres2 (−/−) mice and Cmklr1 (−/−) mice, suggesting a dependency of NK cell recruitment on the chemerin–CMKLR1 axis in melanoma. Despite comparable melanoma growth detected in wild‐type mice and Cmklr1 (−/−) mice, lack of CMKLR1 partially abrogated the melanoma‐inhibitory effect of atRA. This may be due to the inability to enhance tumor‐infiltrating NK cells in Cmklr1 (−/−) mice following atRA treatment. Collectively, our study suggests that down‐regulation of chemerin could be a strategy used by cancers such as melanoma to impair anti‐tumor NK cell immunity and identifies a new anti‐tumor mechanism of atRA by up‐regulating chemerin to enhance CMKLR1‐dependent NK cell recruitment.
Databáze:	OpenAIRE
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