Journal
CANCER IMMUNOLOGY RESEARCH
Volume 7, Issue 11, Pages 1775-1788Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0168
Keywords
-
Categories
Funding
- Italian Association for Cancer Research (AIRC) [721-19014, 9962, 21147, IG-20776]
- Fondazione Berlucchi
- Interuniversity Attraction Poles (IAP) program [7-40]
- European Commission (ERC) [PHII-669415]
- European Commission (FP7 project) [281608 TIMER]
- European Commission (ESA/ITN) [H2020-MSCAITN-2015-676129]
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [FIRB RBAP11H2R9]
- Italian Ministry of Health
- Fondazione Italiana Ricerca sul Cancro (FIRC)
- Fondazione Veronesi
Ask authors/readers for more resources
CCRL2 is a nonsignaling seven-transmembrane domain receptor. CCRL2 binds chemerin, a protein that promotes chemotaxis of leukocytes, including macrophages and natural killer (NK) cells. In addition, CCRL2 controls the inflammatory response in different pathologic settings, such as hypersensitivity, inflammatory arthritis, and experimental autoimmune encephalitis. Here, we investigated the role of CCRL2 in the regulation of lung cancer-related inflammation. The genetic deletion of Ccrl2 promoted tumor progression in urethane-induced and in Kras(G12D/+)/p53(LoxP) lung tumor mouse models. Similarly, a Kras-mutant lung tumor displayed enhanced growth in Ccrl2-deficient mice. This phenotype was associated with a reduced inflammatory infiltrate characterized by the impaired recruitment of several leukocyte populations including NK cells. Bone marrow chimeras showed that CCRL2 expression by the nonhematopoietic cell compartment was responsible for the increased tumor formation observed in Kras-mutant Ccrl2-deficient mice. In human and mouse lungs, CCRL2 was expressed by a fraction of CD31(+) endothelial cells, where it could control NK infiltration. Elevated CCRL2 expression in biopsies from human lung adenocarcinoma positively correlated with clinical outcome. These results provide evidence for a crucial role of CCRL2 in shaping an anti-lung tumor immune response.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available