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

• 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.

Subject headings

Medical and Health Sciences  (hsv)

Clinical Medicine  (hsv)

Cancer and Oncology  (hsv)

Medicin och hälsovetenskap  (hsv)

Klinisk medicin  (hsv)

Cancer och onkologi  (hsv)

Keyword

Adjuvant therapy

Colorectal cancer

Innate immunity

Outcome

Tumor associate macrophages