Background: CRC Subtyping Consortium identified 4 molecular subtypes, one of which was classified by factors including activation or expression of immune-related pathways (Guinney J, et al. Nat med 2015). The antitumor activity of cet requires antibody-dependent cell-mediated cytotoxicity (ADCC) driven by natural killer (NK) cells. Strategies to amplify the NK cell activation may improve the efficacy of cet (Kohrt HE, et al. J Clin Invest 2014), suggesting the ADCC activity may be affected by extracellular immune mechanisms. We therefore investigated whether immune-related genes will predict outcome in mCRC patients (pts) treated with cet. Methods: We measured expression levels of 354 immune-related genes implicated in the host immune response to tumors by HTG EdgeSeq Oncology Biomarker Panel, which comprises 2560 gene probes, using next generation sequencing for quantitative analysis of targeted RNAs. Total RNA isolated from tissues of 77 KRAS wild-type pts (57% males, median age of 63 years, 90% of performance status 0, and 15% right-colon cancer) enrolled in 2 phase II trials (JACCRO CC-05:UMIN000004197 or CC-06:UMIN000007022) of 1st-line therapy with FOLFOX or SOX plus cet was analyzed. Univariate Cox regression analysis was performed for all genes that passed QC filtering. Hierarchical clustering was performed using genes under 0.01 of the Cox p-value. Results: In progression-free survival, the clustering using 2 significant genes, RIPK1 and CEACAM5, could divide all participants into 2 groups and the Kaplan-Meier (KM) curve had a significant difference (mean 3.2 vs. 11.7 months, p= 7.61e-08). In overall survival (OS), 2 groups were classified based on the clustering using 7 genes and the KM curves were significantly different (mean 10.8 vs. 26.0 months, p= 5.79e-06). The Cox regression analysis revealed that IRF3 and BMP4 had strong associations with OS (p= 6.02×10^-4, adjusted FDR.p= 0.043 and p= 8.69×10^-4, FDR.p= 0.043, respectively). Conclusions: Our study demonstrates that immune-related genes may identify subtypes associated with clinical outcome of 1st-line cet treatment for mCRC. Further studies to validate the findings are warranted.