title: Chronic intake of high fish oil diet induces myeloid-derived suppressor cells to promote tumor growth.
abstract: Omega-3 polyunsaturated fatty acids enriched fish oil exerts beneficial anti-inflammatory effects in animal models with acute and chronic inflammatory diseases. Myeloid-derived suppressor cells (MDSCs), comprised of myeloid progenitors and precursors of myeloid cells, play vital roles in cancer. How fish oil affects the generation of MDSCs and the tumor development remains largely unexplored. Here, we show that dietary intake of high fish oil diet suppresses CD8(+) T cells activation and proliferation in vivo via elevated levels of MDSCs. Mechanistically, high fish oil diet induces the expression of immunosuppressive cytokine IL-10 and promotes myelopoiesis in the spleen as well as other peripheral tissues. The immature myeloid cells in the spleen exhibit morphological and functional characteristics of MDSCs with the capability to downregulate CD8(+) T cells activation. Depletion of MDSCs using anti-Gr-1 antibody decreases the growth of subcutaneously transferred B16 melanoma in mice on high fish oil diet. Interestingly, diet-induced production of MDSCs is not solely dependent of the spleen, as splenectomy has no effect on the tumor progress. Our data show that the liver functions as an alternative extramedullary hematopoiesis organ to support MDSCs differentiation and maintain tumor growth. Taken together, our study provides a novel insight into the physiological effects of fish oil and points to MDSCs as a possible mediator linking dietary fish oil intake and immunosuppression in cancer immunosurveillance.
authors.affiliation: Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, 1519 Medical Building, Xuefu Road 301, Zhenjiang, 212013, Jiangsu, China, xiasheng1519@163.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xia
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Cheng
authors.forename: Mutian
authors.initials: M
authors.lastname: Han
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.forename: Qixiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D016827:CD8 Antigens / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000009:adverse effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013156:Splenectomy / Q000379:methods
chemical_list: D016827:CD8 Antigens; D015525:Fatty Acids, Omega-3