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

Alberto Malesci, Paolo Bianchi, Giuseppe Celesti, Gianluca Basso, Federica Marchesi, Fabio Grizzi, Giuseppe Di Caro, Tommaso Cavalleri, Lorenza Rimassa, Richard Palmqvist, Alessandro Lugli, Viktor H. Koelzer, Massimo Roncalli, Alberto Mantovani, Shuji Ogino, Luigi Laghi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere1342918
JournalOncoImmunology
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2 2017

Keywords

  • Adjuvant therapy
  • Colorectal cancer
  • Innate immunity
  • Outcome
  • Tumor associate macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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