title: Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ω6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells.
abstract: Obesity is a low-grade chronic inflammatory state representing an important risk factor for colorectal cancer (CRC). Adipocytes strongly contribute to inflammation by producing inflammatory mediators. In this study we investigated the role of human visceral fat adipocytes in regulating the functions of innate immunity cells. Adipocyte-conditioned media (ACM) from obese (n = 14) and CRC (lean, n = 14; obese, n = 13) subjects released higher levels of pro-inflammatory/immunoregulatory factors as compared to ACM from healthy lean subjects (n = 13). Dendritic cells (DC), differentiated in the presence of ACM from obese and CRC subjects, expressed elevated levels of the inhibitory molecules PD-L1 and PD-L2, and showed a reduced IL-12/IL-10 ratio in response to both TLR ligand- and γδ T lymphocyte-induced maturation. Furthermore, CRC patient-derived ACM inhibited DC-mediated γδ T cell activation. The immunosuppressive signals delivered by ACM from obese and CRC individuals were associated with a pro-inflammatory secretory and ω6 polyunsaturated fatty acid profile of adipocytes. Interestingly, STAT3 activation in adipocytes correlated with dihomo-γlinolenic acid content and was further induced by arachidonic acid, which conversely down-modulated PPARγ. These results provide novel evidence for a cross-talk between human adipocytes and innate immunity cells whose alteration in obesity and CRC may lead to immune dysfunctions, thus setting the basis for cancer development.
authors: Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Manuela
authors: M
authors: Del Cornò
authors: Departments of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors: Massimo
authors: M
authors: D'Archivio
authors: Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Lucia
authors: L
authors: Conti
authors: Departments of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors: Beatrice
authors: B
authors: Scazzocchio
authors: Departments of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors: Rosaria
authors: R
authors: Varì
authors: Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Gloria
authors: G
authors: Donninelli
authors: Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Barbara
authors: B
authors: Varano
authors: Departments of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors: Stefania
authors: S
authors: Giammarioli
authors: Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Simone
authors: S
authors: De Meo
authors: Department of Medical-Surgical Sciences and Biotecnologies, Sapienza University of Rome, Rome, Italy.
authors: Gianfranco
authors: G
authors: Silecchia
authors: General Surgery Unit, Catholic University, Rome, Italy.
authors: Francesco
authors: F
authors: Pennestrì
authors: General Surgery Unit, Catholic University, Rome, Italy.
authors: Roberto
authors: R
authors: Persiani
authors: Departments of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors: Roberta
authors: R
authors: Masella
authors: Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Sandra
authors: S
authors: Gessani
mesh_terms: D017667:Adipocytes / Q000737:chemistry* / Q000166:cytology; D016718:Arachidonic Acid / Q000737:chemistry; D018925:Chemokines / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D018450:Disease Progression; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D007249:Inflammation; D050152:Intra-Abdominal Fat / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D047495:PPAR gamma; D016692:Receptors, Antigen, T-Cell, gamma-delta; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016718:Arachidonic Acid
keywords: adipose tissue; colorectal cancer; fatty acids; immune cells; obesity