Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcome of bevacizumab (bev)-based treatment in patients with metastatic colorectal cancer (mCRC): Results from TRIBE and FIRE3 trials.

3552 Background: TAMs with the M2-like phenotype are regulated by NF-kB pathway including TBK1, which can influence tumor progression by secretion of proangiogenic factors and tumor promoting cytokines, such as VEGF-A and CCL18. These factors drive tumor angiogenesis, migration and immunosuppression. The CCL2/CCR2 axis, histidine-rich glycoprotein (HRG), PIGF and VEGF play a critical role in the polarization of M1 and M2 phenotypes and the recruitment of TAMs to tumor microenvironment. We hypothesized that genes involved in regulating TAMs may predict outcome of bev-based therapy in patients (pts) with mCRC. Methods: We analyzed genomic DNA extracted from blood or tumor samples of pts receiving bev plus FOLFIRI in 2 prospective trials, using PCR-based direct sequencing. Eleven functional polymorphisms in 7 genes (CCL2, CCR2, HRG, PIGF, NFKB1, TBK1 and CCL18) were tested for associations with clinical outcome in a discovery cohort of 228 pts (male 61%, median age 60, follow-up time 27 months [m]) enrolled ...