CCRL2 is a non-signaling seven-transmembrane domain receptor. CCRL2 binds chemerin, a protein that promotes chemotaxis of leukocytes, including macrophages and NK cells. In addition, CCRL2 controls the inflammatory response in different pathological 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 KrasG12D/+/p53LoxP 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 non-hematopoietic 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 provided evidence for a crucial role of CCRL2 in shaping an anti-lung tumor immune response.

The atypical receptor CCRL2 is essential for lung cancer immune surveillance / Del Prete, Annalisa; Sozio, Francesca; Schioppa, Tiziana; Ponzetta, Andrea; Vermi, William; Calza, Stefano; Bugatti, Mattia; Salvi, Valentina; Bernardini, Giovanni; Benvenuti, Federica; Vecchi, Annunciata; Bottazzi, Barbara; Mantovani, Alberto; Sozzani, Silvano. - In: CANCER IMMUNOLOGY RESEARCH. - ISSN 2326-6066. - 7:11(2019), pp. 1775-1788. [10.1158/2326-6066.CIR-19-0168]

The atypical receptor CCRL2 is essential for lung cancer immune surveillance

Sozio, Francesca;Bernardini, Giovanni;Sozzani, Silvano
2019

Abstract

CCRL2 is a non-signaling seven-transmembrane domain receptor. CCRL2 binds chemerin, a protein that promotes chemotaxis of leukocytes, including macrophages and NK cells. In addition, CCRL2 controls the inflammatory response in different pathological 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 KrasG12D/+/p53LoxP 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 non-hematopoietic 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 provided evidence for a crucial role of CCRL2 in shaping an anti-lung tumor immune response.
2019
c c chemokine receptor like 2; CD11b antigen; CD27 antigen
01 Pubblicazione su rivista::01a Articolo in rivista
The atypical receptor CCRL2 is essential for lung cancer immune surveillance / Del Prete, Annalisa; Sozio, Francesca; Schioppa, Tiziana; Ponzetta, Andrea; Vermi, William; Calza, Stefano; Bugatti, Mattia; Salvi, Valentina; Bernardini, Giovanni; Benvenuti, Federica; Vecchi, Annunciata; Bottazzi, Barbara; Mantovani, Alberto; Sozzani, Silvano. - In: CANCER IMMUNOLOGY RESEARCH. - ISSN 2326-6066. - 7:11(2019), pp. 1775-1788. [10.1158/2326-6066.CIR-19-0168]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1371578
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