Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications.

Publisher: Hindawi Publishing Corporation Country of Publication: Egypt NLM ID: 101627166 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-7156 (Electronic) Linking ISSN: 23147156 NLM ISO Abbreviation: J Immunol Res Subsets: MEDLINE

Original Publication: Cairo, Egypt : Hindawi Publishing Corporation, [2014]-

Breast Neoplasms/*immunology ; Immunotherapy/*methods ; Killer Cells, Natural/*immunology ; Obesity/*immunology; Adipokines/metabolism ; Adipose Tissue/metabolism ; Animals ; Breast Neoplasms/complications ; Breast Neoplasms/therapy ; Cytokines/metabolism ; Disease Models, Animal ; Female ; Humans ; Immunity, Innate ; Killer Cells, Natural/metabolism ; Leptin/metabolism ; Lymphocyte Activation ; Obesity/complications ; Obesity/metabolism ; Resistin/metabolism ; Tumor Microenvironment/immunology

Natural killer cells (NK cells) are a crucial constituent of the innate immune system as they mediate immunity against viruses, bacteria, parasites, and most importantly, tumor cells. The exact mechanism of how the innate immune system and specifically NK cells interact with cancer cells is complex and is yet to be understood. Several factors that constitute the tumor microenvironment (TME) such as hypoxia and TGF- β are believed to play a role in the complex physiological reaction of NK cells to tumor cells. On the other hand, several risk factors are implicated in the development and progression of breast cancer, most importantly: obesity. Cytokines released from adipose tissue such as adipokines, leptin, and resistin, among others, are also believed to facilitate tumor progression. In this study, we aimed to build a triad of breast cancer, obesity, and NK cell dysfunction to elucidate a link between these pillars on a cellular level. Directing efforts towards solidifying the link between these factors will help in designing a targeted immunotherapy with a low side-effect profile that can revolutionize breast cancer treatment and improve survival in obese patients.
Competing Interests: The authors declare no conflict of interest.
(Copyright © 2021 Esraa Elaraby et al.)

Gastroenterology. 2020 May;158(6):1713-1727. (PMID: 31972238)
Cell Rep. 2016 Apr 12;15(2):336-48. (PMID: 27050512)
Front Immunol. 2020 Aug 28;11:1989. (PMID: 32983138)
Nat Immunol. 2015 Apr;16(4):376-85. (PMID: 25729921)
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10656-61. (PMID: 21670276)
JCI Insight. 2017 Dec 21;2(24):. (PMID: 29263296)
J Immunol. 2014 Nov 1;193(9):4477-84. (PMID: 25261477)
Nat Immunol. 2008 May;9(5):495-502. (PMID: 18425106)
Regul Pept. 2008 Nov 29;151(1-3):26-34. (PMID: 18556075)
Immunity. 2016 Aug 16;45(2):428-41. (PMID: 27496734)
Immune Netw. 2020 Mar 09;20(2):e14. (PMID: 32395366)
Int J Mol Sci. 2019 Sep 07;20(18):. (PMID: 31500313)
Blood. 2007 May 1;109(9):3812-9. (PMID: 17255361)
J Virol. 2015 Aug;89(15):7922-31. (PMID: 25995253)
Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E108-16. (PMID: 21952038)
Clin Cancer Res. 2009 Jan 15;15(2):425-30. (PMID: 19147746)
Curr Opin Immunol. 2018 Apr;51:170-180. (PMID: 29653339)
Nat Commun. 2017 Oct 11;8(1):864. (PMID: 29021522)
Obes Surg. 2003 Feb;13(1):49-57. (PMID: 12630613)
Nat Immunol. 2018 Dec;19(12):1330-1340. (PMID: 30420624)
Cell Rep. 2013 Nov 14;5(3):637-45. (PMID: 24210818)
Surg Oncol Clin N Am. 2018 Jan;27(1):95-120. (PMID: 29132568)
Front Immunol. 2018 Jun 21;9:1229. (PMID: 29977235)
Lancet. 2014 Aug 30;384(9945):755-65. (PMID: 25129328)
Science. 2011 Jan 7;331(6013):44-9. (PMID: 21212348)
Int J Cell Biol. 2012;2012:340296. (PMID: 22272201)
Nature. 1998 Feb 19;391(6669):795-9. (PMID: 9486650)
Clin Transl Oncol. 2019 Feb;21(2):117-125. (PMID: 29916188)
Proc Nutr Soc. 2008 May;67(2):128-45. (PMID: 18412987)
Front Immunol. 2017 Sep 13;8:1124. (PMID: 28955340)
Expert Opin Biol Ther. 2017 Mar;17(3):313-324. (PMID: 27960589)
Breast Cancer Res. 2019 Mar 1;21(1):35. (PMID: 30823902)
Genes Dev. 2018 Oct 1;32(19-20):1267-1284. (PMID: 30275043)
Cell. 2016 Mar 24;165(1):45-60. (PMID: 27015306)
Int J Mol Sci. 2014 Apr 11;15(4):6184-223. (PMID: 24733068)
Nature. 2001 Sep 13;413(6852):165-71. (PMID: 11557981)
J Clin Oncol. 2016 Dec 10;34(35):4270-4276. (PMID: 27903155)
Curr Oncol Rep. 2016 Sep;18(9):56. (PMID: 27475805)
Oncologist. 2016 Apr;21(4):404-17. (PMID: 26865587)
Front Immunol. 2017 Nov 07;8:1486. (PMID: 29163547)
J Nutr Metab. 2017;2017:4297025. (PMID: 28357137)
Sci Rep. 2017 Feb 15;7:42665. (PMID: 28198418)
Medicina (Kaunas). 2019 Dec 30;56(1):. (PMID: 31906017)
Methods Enzymol. 2014;537:17-30. (PMID: 24480339)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
Obes Surg. 2011 Jan;21(1):112-8. (PMID: 20803097)
Prz Menopauzalny. 2015 Sep;14(3):196-202. (PMID: 26528110)
JCI Insight. 2016 Jul 21;1(11):e85560. (PMID: 27699222)
Nat Med. 2009 Aug;15(8):914-20. (PMID: 19633658)
J Exp Med. 1989 Jun 1;169(6):2233-8. (PMID: 2471777)
Nature. 2000 Aug 17;406(6797):747-52. (PMID: 10963602)
ScientificWorldJournal. 2013 Nov 14;2013:630869. (PMID: 24348178)
J Clin Invest. 2011 Jun;121(6):2094-101. (PMID: 21633177)
J Allergy Clin Immunol. 2013 Sep;132(3):515-525. (PMID: 23993353)
Obesity (Silver Spring). 2015 Nov;23(11):2233-41. (PMID: 26390898)
Ageing Res Rev. 2013 Sep;12(4):1069-78. (PMID: 23660515)
Semin Immunol. 2017 Jun;31:20-29. (PMID: 28888619)
Adv Exp Med Biol. 2005;560:47-50. (PMID: 15932019)
J Gen Intern Med. 2004 Apr;19(4):324-31. (PMID: 15061741)
Clin Cancer Res. 2004 Aug 15;10(16):5367-74. (PMID: 15328174)
Endocrine. 2010 Aug;38(1):104-12. (PMID: 20960110)
Adv Exp Med Biol. 2007;608:1-22. (PMID: 17993229)
Cell Metab. 2016 Apr 12;23(4):685-98. (PMID: 27050305)
Endocrinology. 2008 Jul;149(7):3370-8. (PMID: 18356278)
Int J Health Sci (Qassim). 2014 Jan;8(1):79-83. (PMID: 24899882)
Curr Pharm Des. 2015;21(10):1301-10. (PMID: 25506895)
Blood. 2014 Jun 19;123(25):3855-63. (PMID: 24719405)
Science. 2013 Nov 29;342(6162):1094-8. (PMID: 24288332)
Front Immunol. 2020 Mar 13;11:245. (PMID: 32231659)
Oncoimmunology. 2014 Aug 03;3(8):e952197. (PMID: 25610741)
Trends Immunol. 2001 Nov;22(11):633-40. (PMID: 11698225)
Int Immunol. 2001 Apr;13(4):459-63. (PMID: 11282985)
J Immunol. 2013 Jan 15;190(2):712-22. (PMID: 23241894)
J Am Diet Assoc. 2004 Jun;104(6):903-12. (PMID: 15175588)
J Cancer Prev. 2017 Dec;22(4):260-266. (PMID: 29302585)
Immunol Res. 2018 Apr;66(2):234-244. (PMID: 29560551)
Leukemia. 2018 Feb;32(2):520-531. (PMID: 28725044)
J Cell Physiol. 2013 Jun;228(6):1202-9. (PMID: 23129404)
Med Sci Sports Exerc. 1998 Dec;30(12):1666-71. (PMID: 9861597)
Leukemia. 1994 Apr;8(4):652-8. (PMID: 8152260)
Hypoxia (Auckl). 2015 Dec 11;3:83-92. (PMID: 27774485)
Adv Exp Med Biol. 2017;1024:225-244. (PMID: 28921473)
Blood. 2010 Mar 18;115(11):2167-76. (PMID: 19965656)
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74. (PMID: 11553815)
Arch Intern Med. 1998 Sep 28;158(17):1855-67. (PMID: 9759681)
Cancer Discov. 2016 Jun;6(6):630-49. (PMID: 27072748)
Clin Immunol. 2017 Apr;177:12-17. (PMID: 26794911)
Hematol Oncol Stem Cell Ther. 2015 Jun;8(2):47-55. (PMID: 25571788)
Mol Carcinog. 2015 Jan;54(1):58-71. (PMID: 24038423)
Cancer Cell. 2017 Aug 14;32(2):135-154. (PMID: 28810142)
J Nutr Biochem. 2004 Jul;15(7):418-25. (PMID: 15219927)
Nat Immunol. 2017 Nov;18(11):1197-1206. (PMID: 28920951)
Trends Mol Med. 2013 Aug;19(8):487-500. (PMID: 23746697)
Immunology. 2009 Apr;126(4):458-65. (PMID: 19278419)
J Exp Med. 2012 Sep 24;209(10):1869-82. (PMID: 22927549)
Nat Immunol. 2017 Sep;18(9):1004-1015. (PMID: 28759001)
J Clin Invest. 2013 Oct;123(10):4479-88. (PMID: 24091329)
Nat Immunol. 2008 May;9(5):503-10. (PMID: 18425107)
Diabetes Metab. 2008 Feb;34(1):2-11. (PMID: 18093861)
Oncoimmunology. 2016 Sep 20;5(12):e1235106. (PMID: 28151533)

0 (Adipokines)
0 (Cytokines)
0 (Leptin)
0 (Resistin)

Date Created: 20210702 Date Completed: 20211215 Latest Revision: 20240402

20240402

PMC8205589

10.1155/2021/9972927

34212054