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Body composition of the host influences dendritic cell phenotype in patients treated for colorectal cancer

  • Original Article
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Tumor Biology

Abstract

Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = −0.46, p = 0.03.) and with CD83 [all DCs (r = −0.63; p = 0.01) and myeloid DCs (r = −0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC.

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References

  1. Legitimo A, Consolini R, Failli A, Orsini G, Spisni R. Dendritic cell defects in the colorectal cancer. Human Vaccin Immunother. 2014;10:3224–35.

    Article  Google Scholar 

  2. Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 2010;16:880–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. O’Shea D, Corrigan M, Dunne MR, Jackson R, Woods C, Gaoatswe G, et al. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection. Int J Obes. 2013;37:1510–3.

    Article  Google Scholar 

  4. Orsini G, Legitimo A, Failli A, Massei F, Biver P, Consolini R. Enumeration of human peripheral blood dendritic cells throughout the life. Int Immunol. 2012;24:347–56.

    Article  CAS  PubMed  Google Scholar 

  5. Clatworthy MR, Aronin CE, Mathews RJ, Morgan NY, Smith KG, Germain RN. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes. Nat Med. 2014;20:1458–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fricke I, Gabrilovich DI. Dendritic cells and tumor microenvironment: a dangerous liaison. Immunol Investig. 2006;35:459–83.

    Article  CAS  Google Scholar 

  7. Ma Y, Shurin GV, Peiyuan Z, Shurin MR. Dendritic cells in the cancer microenvironment. J Cancer. 2013;4:36–44.

    Article  CAS  PubMed  Google Scholar 

  8. Yuan A, Steigen SE, Goll R, Vonen B, Husbekk A, Cui G, et al. Dendritic cell infiltration pattern along the colorectal adenoma-carcinoma sequence. APMIS. 2008;116:445–56.

    Article  CAS  PubMed  Google Scholar 

  9. Thibault R, Pichard C. The evaluation of body composition: a useful tool for clinical practice. Ann Nutr Metab. 2012;60:6–16.

    Article  CAS  PubMed  Google Scholar 

  10. Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33:997–1006.

    Article  PubMed  Google Scholar 

  11. Doyle SL, Bennett AM, Donohoe CL, Mongan AM, Howard JM, Lithander FE, et al. Establishing computed tomography-defined visceral fat area thresholds for use in obesity-related cancer research. Nutr Res. 2013;33:171–9.

    Article  CAS  PubMed  Google Scholar 

  12. Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9:629–35.

    Article  PubMed  Google Scholar 

  13. Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013;31:1539–47.

    Article  PubMed  Google Scholar 

  14. Wronska A, Kmiec Z. Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiol. 2012;205:194–208.

    Article  CAS  Google Scholar 

  15. Aubrey J, Esfandiari N, Baracos VE, Buteau FA, Frenette J, Putman CT, et al. Measurement of skeletal muscle radiation attenuation and basis of its biological variation. Acta Physiol. 2014;210:489–97.

    Article  CAS  Google Scholar 

  16. Miljkovic I, Zmuda JM. Epidemiology of myosteatosis. Curr Opin Clin Nutr Metab Care. 2010;13:260–4.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Malietzis G, Johns N, Al-Hassi HO, Knight SC, Kennedy RH, Fearon KC, et al. Low muscularity and myosteatosis is related to the host systemic inflammatory response in patients undergoing surgery for colorectal cancer. Ann Surg. 2016;263:320–5.

    Article  PubMed  Google Scholar 

  18. Malietzis G, Aziz O, Bagnall NM, Johns N, Fearon KC, Jenkins JT. The role of body composition evaluation by computerized tomography in determining colorectal cancer treatment outcomes: a systematic review. Eur J Surg Oncol. 2015;41:186–96.

    Article  CAS  PubMed  Google Scholar 

  19. Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol. 2014;222:R113–27.

    Article  CAS  PubMed  Google Scholar 

  20. Macia L, Delacre M, Abboud G, Ouk TS, Delanoye A, Verwaerde C, et al. Impairment of dendritic cell functionality and steady-state number in obese mice. J Immunol. 2006;177:5997–6006.

    Article  CAS  PubMed  Google Scholar 

  21. Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA. Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology. 2009;126:268–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Stefanyk LE, Dyck DJ. The interaction between adipokines, diet and exercise on muscle insulin sensitivity. Curr Opin Clin Nutr Metab Care. 2010;13:255–9.

    Article  CAS  PubMed  Google Scholar 

  23. Lutz CT, Quinn LS. Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism. Aging. 2012;4:535–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Quinn LS. Interleukin-15: a muscle-derived cytokine regulating fat-to-lean body composition. J Anim Sci. 2008;86:E75–83.

    Article  CAS  PubMed  Google Scholar 

  25. Riechman SE, Balasekaran G, Roth SM, Ferrell RE. Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J Appl Physiol. 2004;97:2214–9.

    Article  CAS  PubMed  Google Scholar 

  26. Anguille S, Lion E, Van den Bergh J, Van Acker HH, Willemen Y, Smits EL, et al. Interleukin-15 dendritic cells as vaccine candidates for cancer immunotherapy. Human Vaccin Immunother. 2013;9:1956–61.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC) (BBSRC Strategic Programme for Gut Health and Food Safety to the Institute for Food Research BB/J004529/1).

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Authors and Affiliations

  1. Antigen Presentation Research Group, Imperial College London, North West London Hospitals Campus, Watford Road, Harrow, HA1 3UJ, UK

    George Malietzis, Gui Han Lee, Hafid O. Al-Hassi, David Bernardo & Stella C. Knight

  2. Department of Surgery, St. Mark’s Hospital, Watford Road, Harrow Middlesex, HA1 3UJ, UK

    George Malietzis, Gui Han Lee, Robin H. Kennedy & John T. Jenkins

  3. Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, 28006, Spain

    David Bernardo

  4. Section of Investigative Medicine, Division of Diabetes, Endocrinology, and Metabolism, Faculty of Medicine|, Imperial College, London, W12 0NN, UK

    Alexandra I. F. Blakemore

  5. Department of Life Sciences, Brunel University London, Middlesex, UB8 3PH, UK

    Alexandra I. F. Blakemore

  6. Department of Histopathology, St. Mark’s Hospital, Watford Road, Harrow Middlesex, HA1 3UJ, UK

    Morgan Moorghen

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  1. George Malietzis
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  2. Gui Han Lee
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  3. Hafid O. Al-Hassi
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  4. David Bernardo
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  5. Alexandra I. F. Blakemore
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  6. Robin H. Kennedy
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  7. Morgan Moorghen
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  8. John T. Jenkins
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  9. Stella C. Knight
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Correspondence to Stella C. Knight.

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Malietzis, G., Lee, G.H., Al-Hassi, H.O. et al. Body composition of the host influences dendritic cell phenotype in patients treated for colorectal cancer. Tumor Biol. 37, 11359–11364 (2016). https://doi.org/10.1007/s13277-016-5009-y

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  • DOI: https://doi.org/10.1007/s13277-016-5009-y

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