Radiation-driven lipid accumulation and dendritic cell dysfunction in cancer.
Dendritic cells (DCs) play important roles in the initiation and maintenance of the immune response. The dysfunction of DCs contributes to tumor evasion and growth. Here we report our findings on the dysfunction of DCs in radiation-induced thymic lymphomas, and the up-regulation of the expression of the lipoprotein lipase (LPL) and the fatty acid binding protein (FABP4), and the level of triacylglycerol (TAG) in serum after total body irradiation, which contribute to DCs lipid accumulation. DCs with high lipid content showed low expression of co-stimulatory molecules and DCs-related cytokines, and were not able to effectively stimulate allogeneic T cells. Normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the function of DCs. A high-fat diet promoted radiation-induced thymic lymphoma growth. In all, our study shows that dysfunction of DCs in radiation-induced thymic lymphomas was due to lipid accumulation and may represent a new mechanism in radiation-induced carcinogenesis.
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Fu
F
Gao
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Cong
C
Liu
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Jiaming
J
Guo
National Key Laboratory of Medical Immunology &Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Weimin
W
Sun
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Linfeng
L
Xian
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Dongchen
D
Bai
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Hu
H
Liu
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Ying
Y
Cheng
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Bailong
B
Li
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Jianguo
J
Cui
Department of Centre for Disease Prevention and Control, Chengdu Military Region, Chengdu610021, China.
Chaoxiong
C
Zhang
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Jianming
J
Cai
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D063646:Carcinogenesis / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005720:Gamma Rays / Q000009:adverse effects*; D050356:Lipid Metabolism / Q000528:radiation effects*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008223:Lymphoma / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D013953:Thymus Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000528:radiation effects
D016207:Cytokines; D050556:Fatty Acid-Binding Proteins; D014280:Triglycerides; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase