Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer.

Malesci, Alberto; Bianchi, Paolo; Celesti, Giuseppe; Basso, Gianluca; Marchesi, Federica; Grizzi, Fabio; Di Caro, Giuseppe; Cavalleri, Tommaso; Rimassa, Lorenza; Palmqvist, Richard; Lugli, Alessandro; Kölzer, Viktor; Roncalli, Massimo; Mantovani, Alberto; Ogino, Shuji; Laghi, Luigi (2017). Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer. Oncoimmunology, 6(12), e1342918. Landes Bioscience 10.1080/2162402X.2017.1342918

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Kölzer, Viktor

ISSN:

2162-4011

Publisher:

Landes Bioscience

Language:

English

Submitter:

Alessandro Lugli

Date Deposited:

12 Feb 2018 15:04

Last Modified:

23 Oct 2019 16:05

Publisher DOI:

10.1080/2162402X.2017.1342918

PubMed ID:

29209561

Uncontrolled Keywords:

Adjuvant therapy Colorectal cancer Innate immunity Outcome Tumor associate macrophages

BORIS DOI:

10.7892/boris.110697

URI:

https://boris.unibe.ch/id/eprint/110697

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