Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer. (2nd December 2017)

• Record Type: Journal Article
• Authors: Malesci, Alberto; Bianchi, Paolo; Celesti, Giuseppe; Basso, Gianluca; Marchesi, Federica; Grizzi, Fabio; Di Caro, Giuseppe; Cavalleri, Tommaso; Rimassa, Lorenza; Palmqvist, Richard; Lugli, Alessandro; Koelzer, Viktor. H.; Roncalli, Massimo; Mantovani, Alberto; Ogino, Shuji; Laghi, Luigi
• Is Part Of: Oncoimmunology. Volume 6:Number 12(2017)
• Publication Date: 2017-12-02
• Subjects: Adjuvant therapy -- Colorectal cancer -- Innate immunity -- Outcome -- Tumor associate macrophages; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1342918
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.