ω-6 polyunsaturated fatty acids derived lipid mediators promote colorectal cancer growth by providing an immunosuppressive microenvironment

Long-chain polyunsaturated fatty acids (PUFAs) are enzymatically synthesized to generate lipid mediators (LMs). PUFAs metabolism is an important factor in the development of colorectal cancer (CRC), but the LMs profile and the underlying mechanisms remain unclear. To elucidate the LMs profile in the serum of patients with CRC, forty LMs were quantified by LC-MS/MS based on multiple reaction monitoring (MRM) mode. To further explore PUFAs function in tumor development, Cytometry Time Of Flight (CyTOF) was used to analyze peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TILs) isolated from mouse tumor model raised by low ω-6 PUFAs diets. ω-3 PUFAs derived LMs, such as RvE2 and RvE3 were downregulated in the serum of CRC compared with healthy controls. While some ω-6 PUFAs derived LMs, such as HETE and PGE2 were upregulated. The serum of mouse model showed that ω-6 PUFAs derived LMs, such as PGE2, 6- trans -12-epi LTB4 and 14,15-LTC4, were down-regulated. CyTOF analysis showed that low ω-6 PUFAs diets play an anti-tumor effect by increasing the CD8 + T cells and decreasing CD4 + CD39 + T cells. In conclusion, these results support that low ω-6 PUFAs diets may suppress CRC development by affecting the tumor microenvironment.