Malesci, AlbertoBianchi, PaoloCelesti, GiuseppeBasso, GianlucaMarchesi, FedericaGrizzi, FabioDi Caro, GiuseppeCavalleri, TommasoRimassa, LorenzaPalmqvist, RichardLugli, AlessandroKoelzer, Viktor. H.Roncalli, MassimoMantovani, AlbertoOgino, ShujiLaghi, Luigi2018-01-182017Malesci, A., P. Bianchi, G. Celesti, G. Basso, F. Marchesi, F. Grizzi, G. Di Caro, et al. 2017. “Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer.” Oncoimmunology 6 (12): e1342918. doi:10.1080/2162402X.2017.1342918. http://dx.doi.org/10.1080/2162402X.2017.1342918.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651945ABSTRACT Tumor-associated macrophages (TAMs) play a role in tumor development and progression. We hypothesized that abundance of TAMs might modify efficacy of 5-fluorouracil chemotherapy in colorectal cancer. We measured the density of CD68+ TAMs at the invasive front of primary tumor of colorectal carcinoma (PT-TAMs; n = 208), at available matched metastatic lymph node (LN-TAMs; n = 149), and in an independent set of primary colorectal cancers (PT-TAMs, n = 111). The hazard ratios for disease-free survival were computed by Cox proportional-hazards model. In exploratory analysis, the interaction between TAMs and 5-fluorouracil adjuvant therapy was significant (PT-TAMs, p = 0.02; LN-TAMs, p = 0.005). High TAMs were independently associated with better disease-free survival only in 5-fluorouracil-treated patients (PT-TAMs, HR 0.23; 95%CI, 0.08–0.65; p = 0.005; LN-TAMs, HR 0.13; 95%CI, 0.04–0.43; p = 0.001). The independent predictive value of PT-TAMs was replicated in the external set (HR, 0.14; 95%CI 0.02–1.00; p = 0.05). In an in vitro experiment, 5-fluorouracil and macrophages showed a synergistic effect and increased colorectal cancer cell death. High densities of TAMs, particularly in metastatic lymph-nodes, identify stage III colorectal cancer patients benefitting from 5-fluorouracil adjuvant therapy.en-USAdjuvant therapyColorectal cancerInnate immunityOutcomeTumor associate macrophagesJournal Article2018-01-1810.1080/2162402X.2017.1342918