RT Journal Article SR Electronic T1 Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression JF Cancer Immunology Research JO Cancer Immunol Res FD American Association for Cancer Research SP 578 OP 593 DO 10.1158/2326-6066.CIR-17-0036 VO 6 IS 5 A1 Porta, Chiara A1 Ippolito, Alessandro A1 Consonni, Francesca Maria A1 Carraro, Lorenzo A1 Celesti, Giuseppe A1 Correale, Carmen A1 Grizzi, Fabio A1 Pasqualini, Fabio A1 Tartari, Silvia A1 Rinaldi, Maurizio A1 Bianchi, Paolo A1 Balzac, Fiorella A1 Vetrano, Stefania A1 Turco, Emilia A1 Hirsch, Emilio A1 Laghi, Luigi A1 Sica, Antonio YR 2018 UL http://cancerimmunolres.aacrjournals.org/content/6/5/578.abstract AB Although tumor-associated macrophages (TAM) display a M2-skewed tumor-promoting phenotype in most cancers, in colorectal cancer, both TAM polarization and its impact remain controversial. We investigated the role of the M2-polarizing p50 NF-κB subunit in orchestrating TAM phenotype, tumor microenvironment composition, and colorectal cancer progression. We first demonstrated, by parallel studies in colitis-associated cancer (CAC) and in genetically driven ApcMin mouse models, that the p50-dependent inhibition of M1-polarized gut inflammation supported colorectal cancer development. In accordance with these studies, p50–/– mice displayed exacerbated CAC with fewer and smaller tumors, along with enhanced levels of M1/Th1 cytokines/chemokines, including IL12 and CXCL10, whose administration restrained CAC development in vivo. The inflammatory profile supporting tumor resistance in colons from p50–/– tumor bearers correlated inversely with TAM load and positively with both recruitment of NK, NKT, CD8+ T cells and number of apoptotic tumor cells. In agreement, myeloid-specific ablation of p50 promoted tumor resistance in mice, whereas in colorectal cancer patients, a high number of p50+ TAMs at the invasive margin was associated with decreased IL12A and TBX21 expression and worse postsurgical outcome. Our findings point to p50 involvement in colorectal cancer development, through its engagement in the protumor activation of macrophages, and identify a candidate for prognostic and target therapeutic intervention. Cancer Immunol Res; 6(5); 578–93. ©2018 AACR.