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, 0.08â0.65; p = 0.005; LN-TAMs, HR 0.13; 95%CI, 0.04â0.43; p = 0.001). The independent predictive value of PT-TAMs was replicated in the external set (HR, 0.14; 95%CI 0.02â1.00; 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.
Tumor-associated macrophages and response to 5-flourouracil adjuvant therapy in stage III colorectal cancer / A. Malesci, P. Bianchi, G. Celesti, G. Basso, F. Marchesi, F. Grizzi, G. DI CARO, T. Cavalleri, L. Rimassa, R. Palmqvist, A. Lugli, V....H. Koelzer, M. Roncalli, A. Mantovani, S. Ogino, L. Laghi. - In: ONCOIMMUNOLOGY. - ISSN 2162-4011. - 6:10(2017), pp. e1342918.1-e1342918.11.
|Titolo:||Tumor-associated macrophages and response to 5-flourouracil adjuvant therapy in stage III colorectal cancer|
MALESCI, ALBERTO (Primo)
|Parole Chiave:||Adjuvant therapy; Colorectal cancer; Innate immunity; Outcome; Tumor associate macrophages; Immunology and Allergy; Immunology; Oncology|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
Settore MED/12 - Gastroenterologia
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1080/2162402X.2017.1342918|
|Appare nelle tipologie:||01 - Articolo su periodico|