American Association for Cancer Research
cir-22-0951_supplementary_figures_suppsf1-sf7.pdf (2.25 MB)

Supplementary Figures from CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer

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journal contribution
posted on 2023-09-01, 08:40 authored by Francesca Sozio, Tiziana Schioppa, Mattia Laffranchi, Valentina Salvi, Nicola Tamassia, Francisco M. Bianchetto-Aguilera, Laura Tiberio, Raffaella Bonecchi, Daniela Bosisio, Marc Parmentier, Barbara Bottazzi, Roberto Leone, Eleonora Russo, Giovanni Bernardini, Stefano Garofalo, Cristina Limatola, Angela Gismondi, Giuseppe Sciumè, Alberto Mantovani, Annalisa Del Prete, Silvano Sozzani

Supplementary Figures 1-7 with legends


Fondazione AIRC per la ricerca sul cancro ETS (AIRC)

Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)

Sapienza Università di Roma (Sapienza University of Rome)



Patterns of receptors for chemotactic factors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represents a selective pathway for the homing of natural killer (NK) cells to the lung. C–C motif chemokine receptor-like 2 (CCRL2) is a nonsignaling seven-transmembrane domain receptor able to control lung tumor growth. CCRL2 constitutive or conditional endothelial cell targeted ablation, or deletion of its ligand chemerin, were found to promote tumor progression in a Kras/p53Flox lung cancer cell model. This phenotype was dependent on the reduced recruitment of CD27– CD11b+ mature NK cells. Other chemotactic receptors identified in lung-infiltrating NK cells by single-cell RNA sequencing (scRNA-seq), such as Cxcr3, Cx3cr1, and S1pr5, were found to be dispensable in the regulation of NK-cell infiltration of the lung and lung tumor growth. scRNA-seq identified CCRL2 as the hallmark of general alveolar lung capillary endothelial cells. CCRL2 expression was epigenetically regulated in lung endothelium and it was upregulated by the demethylating agent 5-aza-2′-deoxycytidine (5-Aza). In vivo administration of low doses of 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells, and reduced lung tumor growth. These results identify CCRL2 as an NK-cell lung homing molecule that has the potential to be exploited to promote NK cell–mediated lung immune surveillance.

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