TY - JOUR
T1 - Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer
AU - Malesci, Alberto
AU - Bianchi, Paolo
AU - Celesti, Giuseppe
AU - Basso, Gianluca
AU - Marchesi, Federica
AU - Grizzi, Fabio
AU - Di Caro, Giuseppe
AU - Cavalleri, Tommaso
AU - Rimassa, Lorenza
AU - Palmqvist, Richard
AU - Lugli, Alessandro
AU - Koelzer, Viktor H.
AU - Roncalli, Massimo
AU - Mantovani, Alberto
AU - Ogino, Shuji
AU - Laghi, Luigi
PY - 2017/12/2
Y1 - 2017/12/2
N2 - 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.
AB - 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.
KW - Adjuvant therapy
KW - Colorectal cancer
KW - Innate immunity
KW - Outcome
KW - Tumor associate macrophages
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U2 - 10.1080/2162402X.2017.1342918
DO - 10.1080/2162402X.2017.1342918
M3 - Article
AN - SCOPUS:85025153677
VL - 6
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 12
M1 - e1342918
ER -