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Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer
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2017 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 6, no 12, article id e1342918Article in journal (Refereed) Published
Abstract [en]

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 D 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 D 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.

Place, publisher, year, edition, pages
Taylor & Francis, 2017. Vol. 6, no 12, article id e1342918
Keywords [en]
Adjuvant therapy, Colorectal cancer, Innate immunity, Outcome, Tumor associate macrophages
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-144130DOI: 10.1080/2162402X.2017.1342918ISI: 000419128300015OAI: oai:DiVA.org:umu-144130DiVA, id: diva2:1176378
Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-06-09Bibliographically approved

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