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e15588 Background: The clinical trial Keynote 177 is a breakthrough research in colon rectal cancer (CRC), however, the results of subgroups revealed that immunotherapy did not benefit more than chemotherapy in patients with KRAS mutation. Here we assessed characteristics of tumor immune microenvironment in patients with or without KRAS mutation, to find out the underlying mechanisms that prevent KRAS-mutated CRC patients from benefiting from immunotherapy. Methods: Tumor tissue samples of 77 CRC patients were collected from Janary 2019, several kinds of immune cells including CD8+ T cells, M1/M2 tumor associated macrophages (TAM), CD56bright NK cells and CD56dim NK cells in the tumor tissue were evaluated by multiple fluorescence immunohistochemistry (mIHC), and expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. In addition, gene mutation was detected by means of next generation squesing (NGS). All these detections were performed in a College of American Pathologists (CAP)-certified and Clinical Laboratory Improvement Amendments (CLIA)-accredited lab for gene mutation analysis (3D Medicines Inc.,Shanghai, China). Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.). Results: According to whether KRAS is mutated, these 77 patients were divided into two groups, KRAS wild type (WT) (n = 49) and KRAS mutation group (n = 28). There was no significant difference in the CD8+T cells infiltrated in tumor tissue of KRAS WT and KRAS mutation samples, however, less CD8+ T cells were found in stroma of tumor tissue of KRAS WT samples than in KRAS mutation. What’s more, both the ratio of M1:M2 and CD56dim NK: CD56bright NK cells in the tumor tissues of KRAS WT were significantly higher than in KRAS mutation samples(p < 0.05). No significant difference was found between two groups, while higher MSI-H proportion was found in KRAS mutation group than in KRAS WT (33.4% and 12.5%, respectively). The proportion of positive PD-L1expression (TPS≥1) in both groups is very low, especially, proportion of strong positive (TPS≥50). Conclusions: The different response to immune checkpoint inhibitors therapy for CRC patient with or without KRAS mutation mainly associated with factors of TIME, not only CD8+T cells, but tumor associated macrophages and different sub-population of NK cells should be put into consideration.