Lipid accumulation and dendritic cell dysfunction in cancer.
Herber DL; Cao W; Nefedova Y; Novitskiy SV; Nagaraj S; Tyurin VA; Corzo A; Cho H-I; Celis E; Lennox B; Knight SC; Padhya T; McCaffrey TV; McCaffrey JC; Antonia S; Fishman M; Ferris RL; Kagan VE; Gabrilovich DI
Nat Med 2010 Aug; 16(8):880-886
Dendritic cells (DCs), a type of professional antigen-presenting cells, are responsible for initiation and maintenance of immune responses. Here we report that a substantial proportion of DCs in tumor-bearing mice and people with cancer have high amounts of triglycerides as compared with DCs from tumor-free mice and healthy individuals. In our studies, lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to upregulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of major histocompatibility complex and co-stimulatory molecules. However, lipid-laden DCs had a reduced capacity to process antigens. Pharmacological normalization of lipid abundance in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of cancer vaccines. These findings suggest that immune responses in cancer can be improved by manipulating the lipid levels in DCs.
Cell-function; Immune-reaction; Animals; Humans; Lipids; Tumors; Antigens; Cancer
Dmitry I Gabrilovich, Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA
University of Pittsburgh at Pittsburgh