Oncotarget

Research Papers:

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

Manuela Del Cornò, Massimo D’Archivio, Lucia Conti, Beatrice Scazzocchio, Rosaria Varì, Gloria Donninelli, Barbara Varano, Stefania Giammarioli, Simone De Meo, Gianfranco Silecchia, Francesco Pennestrì, Roberto Persiani, Roberta Masella and Sandra Gessani _

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Oncotarget. 2016; 7:63093-63105. https://doi.org/10.18632/oncotarget.10998

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Abstract

Manuela Del Cornò1,*, Massimo D’Archivio2,*, Lucia Conti1, Beatrice Scazzocchio2, Rosaria Varì2, Gloria Donninelli1, Barbara Varano1, Stefania Giammarioli2, Simone De Meo1, Gianfranco Silecchia3, Francesco Pennestrì4, Roberto Persiani4, Roberta Masella2, Sandra Gessani1

1Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

2Departments of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy

3Department of Medical-Surgical Sciences and Biotecnologies, Sapienza University of Rome, Rome, Italy

4General Surgery Unit, Catholic University, Rome, Italy

*These authors equally contributed to this work

Correspondence to:

Sandra Gessani, email: [email protected]

Keywords: obesity, adipose tissue, fatty acids, immune cells, colorectal cancer

Received: March 04, 2016     Accepted: July 22, 2016     Published: August 01, 2016

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.


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PII: 10998