Tumor-associated Macrophages and Neuroendocrine Differentiation Decrease the Efficacy of Bevacizumab Plus Chemotherapy in Patients With Advanced Colorectal Cancer

In the present study, we investigated the prognostic and predictive role of neuroendocrine differentiation (NED) and tumor-associated macrophage (TAM) infiltration in tumor tissue from patients with advanced colorectal cancer who had received bevacizumab plus chemotherapy.A total of 123 consecutive patients with advanced colorectal cancer who had received bevacizumab plus irinotecan/oxaliplatin-based combination chemotherapy were included in the present study. In addition to the clinicopathologic parameters, the presence of NED and the level of TAM infiltration were studied as covariates for survival analysis.The median patient age was 57 years (range, 30-76 years). The chemotherapy backbone was FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) for 75% of the patients. Univariate analysis showed that only NED and TAM infiltration were significant predictive factors for progression-free survival. Left-sided tumors and low TAM infiltration were favorable factors for overall survival on univariate analysis. However, the TAM level was the only independent prognostic factor for overall survival (hazard ratio, 0.301; 95% confidence interval, 0.102-0.892).Our results suggest that increased TAM infiltration in tumor tissue and NED could decrease the efficacy of bevacizumab plus combination chemotherapy in patients with advanced colorectal cancer. TAM infiltration in the tumor tissue could be used as a biomarker in patients with advanced colorectal cancer receiving bevacizumab plus chemotherapy.