1. Lipid accumulation and dendritic cell dysfunction in cancer
- Author
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Vladimir A. Tyurin, Dmitry I. Gabrilovich, Donna L. Herber, Esteban Celis, Brianna Lennox, Yulia Nefedova, Hyun Ii Cho, Robert L. Ferris, Valerian E. Kagan, Srinivas Nagaraj, Stella C. Knight, Sergey V. Novitskiy, Alex Corzo, Scott J. Antonia, Wei Cao, Tapan A. Padhya, Mayer Fishman, Thomas V. McCaffrey, Judith C. McCaffrey, and Medical Research Council (MRC)
- Subjects
Research & Experimental Medicine ,CELL BIOLOGY ,ACTIVATION ,Mice ,0302 clinical medicine ,Neoplasms ,Tumor Cells, Cultured ,CLASS-A ,POLYUNSATURATED FATTY-ACIDS ,Mice, Knockout ,0303 health sciences ,Mice, Inbred BALB C ,biology ,Fatty Acids ,Scavenger Receptors, Class A ,hemic and immune systems ,MACROPHAGE SCAVENGER RECEPTOR ,General Medicine ,11 Medical And Health Sciences ,3. Good health ,Medicine, Research & Experimental ,lipids (amino acids, peptides, and proteins) ,Life Sciences & Biomedicine ,EXPRESSION ,Boron Compounds ,Biochemistry & Molecular Biology ,Spectrometry, Mass, Electrospray Ionization ,Antigen presentation ,Immunology ,INHIBITION ,chemical and pharmacologic phenomena ,IMMUNITY ,Major histocompatibility complex ,General Biochemistry, Genetics and Molecular Biology ,Article ,MATURATION ,03 medical and health sciences ,Immune system ,Antigen ,Downregulation and upregulation ,ANTIGEN PRESENTATION ,Animals ,Humans ,Scavenger receptor ,030304 developmental biology ,Fluorescent Dyes ,Science & Technology ,Lipid metabolism ,Dendritic cell ,Dendritic Cells ,Lipid Metabolism ,Mice, Inbred C57BL ,ATHEROSCLEROSIS ,biology.protein ,Neoplasm Transplantation ,030215 immunology - Abstract
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.
- Published
- 2010