First Author | Wunderlich CM | Year | 2018 |
Journal | Nat Commun | Volume | 9 |
Issue | 1 | Pages | 1646 |
PubMed ID | 29695802 | Mgi Jnum | J:261943 |
Mgi Id | MGI:6158201 | Doi | 10.1038/s41467-018-03773-0 |
Citation | Wunderlich CM, et al. (2018) Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment. Nat Commun 9(1):1646 |
abstractText | Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and gammadelta T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and gammadelta T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients. |