Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer
نویسندگان
چکیده
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.
منابع مشابه
Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of adjuvant chemotherapy in patients with stage II–III colorectal cancer
Clinically useful predictors of the efficacy of adjuvant chemotherapy following curative colorectal surgery remain to be determined. In the present study, we investigated the clinical utility of the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) as a predictor of the therapeutic response to 5-fluorouracil (5-FU)-based adjuvant chemo-therapy in patients with stage II-III co...
متن کاملAssociation between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer
Objective Although poorly differentiated cluster has been reported to be a useful grading system for predicting prognosis in colorectal cancer, its relationship to chemotherapy efficacy has not been demonstrated. We aimed to investigate the association between poorly differentiated cluster and the efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer. Methods T...
متن کاملIn Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer
PURPOSE We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. MATERIALS AND METHODS Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouraci...
متن کاملMature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study
OBJECTIVE Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV). METHODS Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvan...
متن کاملThymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5-fluorouracil.
PURPOSE Despite adjuvant 5-fluorouracil (5-FU) therapy, approximately 30% of patients with International Union against Cancer stage II and III colorectal cancer develop recurrence. In this study, we determined the prognostic value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer patients treated with adjuvant 5-FU. EXPERIMENTAL DESIGN A re...
متن کامل