Effects of Obesity on Cancer Progression by Affecting the Immune System
,
Abstract
The prevalence of obesity has been increasing in the last few decades, and it is regarded as one of the major health problems in the world. The rising prevalence of obesity in children and adults is a result of eating disorders and the changes related to the modern lifestyle. Obesity alters the adipocytes’ substance secretion, which affects the function of the immune system and leads to obesity-induced inflammation and the development of obesity-related cancers. Altered chemokines, adipokines, and conditions like insulin resistance are most likely related to the impaired immune system in the obesity state. The impaired secretion of adipokines, such as increased leptin and reduction in adiponectin, affects innate immune system antitumor responses after long-term exposure. In addition, changes in chemokines and, consequently, the promotion of insulin resistance create an immunosuppressive environment that debilitates the host to fight against tumor growth, progression, and metastasis. Accordingly, it may increase cancer susceptibility in obese individuals. Thereby, it can be concluded that treatment of obesity will greatly affect the improvement of immune system function and, as a result, may possibly reduce the risk of cancer. The aim of this study is to review the pathways resulting in impaired immune system and inflammation and their link to cancer progression in obesity. Several hypotheses have been proposed to have a critical contribution to the development of obesity-related cancers, such as the function of cytokines, insulin resistance, and NF-κB and senescence changes in obesity. These hypotheses will be discussed later in this article.
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3. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer. 2004;4(1):11-22.
4. Christ A, Latz E. The Western lifestyle has lasting effects on metaflammation. Nat Rev Immunol. 2019;19(5):267-8.
5. Chandra RK. Nutrition and the immune system: an introduction. Am J Clin Nutr. 1997;66(2):460S-3S.
6. Leischner C, Burkard M, Lauer UM, Busch C, Venturelli S, Frank J, et al. Targeting epigenetic 'readers' with natural compounds for cancer prevention and therapy. J Cancer Prev. 2016;25(4):189-200.
7. Sapienza C, Issa JP. Diet, Nutrition, and Cancer Epigenetics. Annu Rev Nutr. 2016;36:665-81.
8. Mayne ST, Playdon MC, Rock CL. Diet, nutrition, and cancer: past, present and future. Nat Rev Clin Oncol. 2016;13(8):504-15.
9. De Rosa V, Galgani M, Santopaolo M, Colamatteo A, Laccetti R, Matarese G. Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function. Semin Immunol. 2015;27(5):300-9.
10. Galgani M, De Rosa V, Matarese G. T cell metabolism and susceptibility to autoimmune diseases. Mol Immunol. 2015;68(2 Pt C):558-63.
11. Hardman WE. Diet components can suppress inflammation and reduce cancer risk. Nutr Res Pract. 2014;8(3):233-40.
12. Nagahashi M, Yamada A, Katsuta E, Aoyagi T, Huang WC, Terracina KP, et al. Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and Breast Cancer Metastasis. Cancer Res. 2018;78(7):1713-25.
13. DeClercq V, McMurray DN, Chapkin RS. Obesity promotes colonic stem cell expansion during cancer initiation. Cancer Lett. 2015;369(2):336-43.
14. Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Bustos M, Martínez JA, Moreno-Aliaga MJ. Role of obesity-associated dysfunctional adipose tissue in cancer: A molecular nutrition approach. Biochim Biophys Acta. 2011;1807(6):664-78.
15. Alvarez-Curto E, Milligan G. Metabolism meets immunity: The role of free fatty acid receptors in the immune system. Biochem Pharmacol.
16. Wrann CD, Laue T, Hubner L, Kuhlmann S, Jacobs R, Goudeva L, et al. Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions. Am J Physiol Endocrinol Metab. 2012;302(1):E108-16.
17. Macciò A, Madeddu C, Mantovani G. Adipose tissue as target organ in the treatment of hormone-dependent breast cancer: new therapeutic perspectives. Obes Rev. 2009;10(6):660-70.
18. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-38.
19. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548-56.
20. Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, inflammation, and cancer. Annu Rev Pathol. 2016;11(1):421-49.
21. Boutens L, Hooiveld GJ, Dhingra S, Cramer RA, Netea MG, Stienstra R. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia. 2018;61(4):942-53.
22. Poh AR, Ernst M. Targeting macrophages in cancer: from bench to bedside. Front Oncol. 2018;8:49.
23. Gilbert CA, Slingerland JM. Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression. Annu Rev Med. 2013;64:45-57.
24. Simpson ER, Brown KA. Minireview: obesity and breast cancer: a tale of inflammation and dysregulated metabolism. Mol Endocrinol (Baltimore, Md). 2013;27(5):715-25.
25. Castoldi A, Naffah de Souza C, Camara NO, Moraes-Vieira PM. The macrophage switch in obesity development. Front Immunol. 2015;6:637.
26. Oishi Y, Manabe I. Integrated regulation of the cellular metabolism and function of immune cells in adipose tissue. Clin Exp Pharmacol Physiol. 2016;43(3):294-303.
27. Mathis D. Immunological goings-on in visceral adipose tissue. Cell Metab. 2013;17(6):851-9.
28. Caspar-Bauguil S, Cousin B, Galinier A, Segafredo C, Nibbelink M, Andre M, et al. Adipose tissues as an ancestral immune organ: site-specific change in obesity. FEBS Lett. 2005;579(17):3487-92.
29. Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol. 2016;12(1):15-28.
30. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175-84.
31. Liao CM, Zimmer MI, Wang CR. The functions of type I and type II natural killer T cells in inflammatory bowel diseases. Inflamm Bowel Dis. 2013;19(6):1330-8.
32. Waldowska M, Bojarska-Junak A, Rolinski J. A brief review of clinical trials involving manipulation of invariant NKT cells as a promising approach in future cancer therapies. Cent Eur J Immunol. 2017;42(2):181-95.
33. Robertson FC, Berzofsky JA, Terabe M. NKT cell networks in the regulation of tumor immunity. Front Immunol. 2014;5:543.
34. Martinez-Santibanez G, Cho KW, Lumeng CN. Imaging white adipose tissue with confocal microscopy. Methods Enzymol. 2014;537:17-30.
35. Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V, et al. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res. 2012;2012:789174.
36. Moreno-Aliaga MJ, Lorente-Cebrian S, Martinez JA. Regulation of adipokine secretion by n-3 fatty acids. Proc Nutr Soc. 2010;69(3):324-32.
37. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev. 2012;33(4):547-94.
38. Schaffler A, Scholmerich J, Buechler C. Mechanisms of disease: adipokines and breast cancer - endocrine and paracrine mechanisms that connect adiposity and breast cancer. Nat Clin Pract Endocrinol Metab. 2007;3(4):345-54.
39. Otake S, Takeda H, Fujishima S, Fukui T, Orii T, Sato T, et al. Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer. World J Gastroenterol. 2010;16(10):1252-7.
40. Macciò A, Madeddu C, Mantovani G. Adipose tissue as target organ in the treatment of hormone-dependent breast cancer: new therapeutic perspectives. Obes Rev. 2009;10(6):660-70.
41. Romeo J, Martinez-Gomez D, Diaz LE, Gomez-Martinez S, Marti A, Martin-Matillas M, et al. Changes in cardiometabolic risk factors, appetite-controlling hormones and cytokines after a treatment program in overweight adolescents: preliminary findings from the EVASYON study. Pediatr Diabetes. 2011;12(4 Pt 2):372-80.
42. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol (Lond). 2010;6(3):457-70.
43. Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413-37.
44. Saucillo DC, Gerriets VA, Sheng J, Rathmell JC, Maciver NJ. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J Immunol. 2014;192(1):136-44.
45. Carbone F, La Rocca C, Matarese G. Immunological functions of leptin and adiponectin. Biochimie. 2012;94(10):2082-8.
46. Tian Z, Sun R, Wei H, Gao B. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun. 2002;298(3):297-302.
47. Vansaun MN. Molecular pathways: adiponectin and leptin signaling in cancer. Clin Cancer Res. 2013;19(8):1926-32.
48. Laue T, Wrann CD, Hoffmann-Castendiek B, Pietsch D, Hubner L, Kielstein H. Altered NK cell function in obese healthy humans. BMC Obes. 2015;2:1.
49. Brunner T, Wasem C, Torgler R, Cima I, Jakob S, Corazza N. Fas (CD95/Apo-1) ligand regulation in T cell homeostasis, cell-mediated cytotoxicity and immune pathology. Semin Immunol. 2003;15(3):167-76.
50. Lowin B, Hahne M, Mattmann C, Tschopp J. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature. 1994;370(6491):650-2.
51. Gupta S, Agrawal A, Agrawal S, Su H, Gollapudi S. A paradox of immunodeficiency and inflammation in human aging: lessons learned from apoptosis. Immun Ageing. 2006;3:5.
52. O'Rourke RW, Metcalf MD, White AE, Madala A, Winters BR, Maizlin II, et al. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue. Int J Obes (2005). 2009;33(9):978-90.
53. Peraldi P, Hotamisligil GS, Buurman WA, White MF, Spiegelman BM. Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J Biol Chem. 1996;271(22):13018-22.
54. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796-808.
55. Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev. 2011;10(3):319-29.
56. Alvarez-Rodriguez L, Lopez-Hoyos M, Munoz-Cacho P, Martinez-Taboada VM. Aging is associated with circulating cytokine dysregulation. Cell Immunol. 2012;273(2):124-32.
57. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498-503.
58. Ghosh S, Ashcraft K. An IL-6 link between obesity and cancer. Front Biosci (Elite Ed). 2013;5:461-78.
59. Zeyda M, Gollinger K, Kriehuber E, Kiefer FW, Neuhofer A, Stulnig TM. Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression. Int J Obes (2005). 2010;34(12):1684-94.
60. Campbell MJ, Tonlaar NY, Garwood ER, Huo D, Moore DH, Khramtsov AI, et al. Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome. Breast Cancer Res Treat. 2011;128(3):703-11.
61. Balistreri CR, Caruso C, Candore G. The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediators Inflamm. 2010;2010:802078.
62. Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18(5):309-24.
63. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5(10):749-59.
64. Wu JT, Kral JG. The NF-kappaB/I-kappaB signaling system: A molecular target in breast cancer therapy. J Surg Res. 2005;123(1):158-69.
65. Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004;6(3):203-8.
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| Files | ||
| Issue | Vol 7, No 4 (2024) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/igj.v7i4.17885 | |
| Keywords | ||
| Obesity Cancer Progression Inflammation Adipokines Cytokines Insulin | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Moallemian Isfahani M, Khozeimeh F, Hekmatdoost A. Effects of Obesity on Cancer Progression by Affecting the Immune System. Immunol Genet J. 2024;7(4):193-202.
