Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients (original) (raw)

Abstract

In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum and liver of patients with the obesity-associated malignancy oesophageal adenocarcinoma (OAC). Furthermore, we assessed the secreted cytokine profile in OAC patient serum, omentum and liver to assess systemic and local inflammation. We observed parallel T cell cytokine profiles and phenotypes in the omentum and liver of OAC patients, in particular CD69+ and inflammatory effector memory T cells. This study reflects similar processes of inflammation and T cell activation in the omentum and liver, and may suggest common targets to modulate pathological inflammation at these sites.

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ACKNOWLEDGMENTS

The authors would like to thank all of the patients attending the Oesophageal Unit at St. James’s Hospital, Dublin, for their participation in this study.

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Authors and Affiliations

  1. Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, St James’s Hospital, Dublin 8, Ireland
    Melissa J. Conroy, Karen C. Galvin, Suzanne L. Doyle, Maria E. Kavanagh, Ann-Marie Mongan, Aoife Cannon, Gillian Y. Moore, John V. Reynolds & Joanne Lysaght
  2. Oesophageal Unit, St. James’s Hospital, Dublin, Ireland
    John V. Reynolds
  3. School of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland
    Suzanne L. Doyle

Authors

  1. Melissa J. Conroy
  2. Karen C. Galvin
  3. Suzanne L. Doyle
  4. Maria E. Kavanagh
  5. Ann-Marie Mongan
  6. Aoife Cannon
  7. Gillian Y. Moore
  8. John V. Reynolds
  9. Joanne Lysaght

Corresponding author

Correspondence toJoanne Lysaght.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This study was funded by the Health Research Board of Ireland Health Research Award HRA_POR/2011/91.

Informed consent was obtained from all individual participants included in the study.

ELECTRONIC SUPPLEMENTARY MATERIAL

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Supplemental Data Figure 1

Representative dotplots showing the gating strategy for surface marker expression and intracellular cytokine expression by T lymphocytes. a (Left-Right): For surface marker quantification, forward scatter and side scatter were first used to gate on lymphocytes, followed by gating of CD8+ CD4- lymphocytes and CD8- CD4+ lymphocytes. CD62L was then quantified as a percentage of either CD8+ CD4- lymphocytes or CD8- CD4+ lymphocytes. b (Left-Right): For intracellular cytokine quantification, forward scatter and side scatter were first used to gate on lymphocyte gate, followed by gating of CD8+ CD3+ lymphocytes and CD8- CD3+ lymphocytes. TNF-α+ cells were then quantified as a percentage of CD8+ CD3+ lymphocytes or CD8- CD3+ lymphocytes. (TIF 295 kb)

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Conroy, M.J., Galvin, K.C., Doyle, S.L. et al. Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients.Inflammation 39, 1729–1736 (2016). https://doi.org/10.1007/s10753-016-0407-2

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