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Oncoimmunology. 2017 Apr 20;6(5):e1312042. doi: 10.1080/2162402X.2017.1312042. eCollection 2017.

Transcriptional factor EB regulates macrophage polarization in the tumor microenvironment.

Oncoimmunology

Liang Fang, Johnie Hodge, Fatma Saaoud, Junfeng Wang, Stephen Iwanowycz, Yuzhen Wang, Yvonne Hui, Trent D Evans, Babak Razani, Daping Fan

Affiliations

  1. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA.
  2. Department of Immunology, Fourth Military Medical University, Xi'an, China.
  3. Cardiovascular Division, Department of Medicine and Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.

PMID: 28638736 PMCID: PMC5468002 DOI: 10.1080/2162402X.2017.1312042

Abstract

Tumor microenvironment (TME) contains a variety of infiltrating immune cells. Among them, tumor-associated macrophages (TAMs) and their alternative activation contribute greatly to the progression of tumors. The mechanisms governing macrophage polarization in the TME are unclear. Here, we show that in TAMs or macrophages under tumor-conditioned medium treatment, the expression of transcription factor EB (TFEB) is reduced and more of the TFEB protein is in an inactive cytosolic form. Transforming growth factor (TGF)-β is identified as a main driving force for the reduced TFEB expression and activity in TAMs via activating ERK signaling. TFEB interference in macrophages significantly enhanced their alternative activation, with reduced expression of MHC-II and co-stimulatory molecule CD80, decreased ability to activate T cells, and increased ability to attract tumor cells. When co-inoculated with tumor cells, macrophages with TFEB knockdown significantly enhanced tumor growth with increased infiltration of M2-like macrophages, reduced infiltration of CD8

Keywords: Breast cancer; TFEB; macrophage; polarization; tumor microenvironment

References

  1. Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1817-26 - PubMed
  2. Autophagy. 2016 Aug 2;12 (8):1240-58 - PubMed
  3. Clin Cancer Res. 2016 Jun 15;22(12 ):2993-3004 - PubMed
  4. Curr Biol. 2016 Aug 8;26(15):1955-64 - PubMed
  5. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1942-52 - PubMed
  6. J Biol Chem. 2007 May 4;282(18):13746-53 - PubMed
  7. J Clin Invest. 2012 Mar;122(3):787-95 - PubMed
  8. Nat Immunol. 2014 Sep;15(9):846-55 - PubMed
  9. Sci Signal. 2012 Jun 12;5(228):ra42 - PubMed
  10. EMBO J. 2011 Jul 29;30(16):3242-58 - PubMed
  11. Proc Soc Exp Biol Med. 1951 Jun;77(2):358-62 - PubMed
  12. Contrib Microbiol. 2006;13:118-37 - PubMed
  13. J Transl Med. 2012 Sep 03;10:183 - PubMed
  14. Nat Immunol. 2006 Oct;7(10):1082-91 - PubMed
  15. Front Immunol. 2014 Nov 28;5:614 - PubMed
  16. Immunity. 2014 Jul 17;41(1):49-61 - PubMed
  17. Immunity. 2014 Jun 19;40(6):896-909 - PubMed
  18. Autophagy. 2015;11(2):271-84 - PubMed
  19. Nat Immunol. 2013 Jan;14(1):61-71 - PubMed
  20. Immunity. 2014 Jun 19;40(6):857-8 - PubMed
  21. Trends Immunol. 2002 Nov;23(11):549-55 - PubMed
  22. J Immunol. 2013 Feb 1;190(3):1285-96 - PubMed
  23. Cancer Res. 2010 Oct 1;70(19):7465-75 - PubMed
  24. Breast Cancer Res Treat. 2014 Nov;148(2):291-302 - PubMed
  25. Nat Immunol. 2015 Jul;16(7):729-36 - PubMed
  26. Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1439-46 - PubMed
  27. Clinics (Sao Paulo). 2012 Aug;67(8):901-6 - PubMed
  28. Cancer Res. 2004 Oct 1;64(19):7022-9 - PubMed
  29. Chem Biol. 2006 Nov;13(11):1235-42 - PubMed
  30. Oncoimmunology. 2016 Sep 9;5(11):e1232223 - PubMed
  31. Scand J Immunol. 2014 May;79(5):305-14 - PubMed
  32. PLoS One. 2015 Mar 19;10(3):e0120819 - PubMed
  33. PLoS One. 2012;7(12):e51525 - PubMed
  34. Cell Death Dis. 2015 Jun 18;6:e1792 - PubMed
  35. Nature. 2015 Aug 20;524(7565):361-5 - PubMed
  36. J Biol Chem. 2002 Apr 26;277(17 ):14884-93 - PubMed
  37. Science. 2011 Jun 17;332(6036):1429-33 - PubMed
  38. Trends Immunol. 2015 Apr;36(4):229-39 - PubMed
  39. Autophagy. 2013 Aug;9(8):1244-6 - PubMed
  40. Lung Cancer. 2015 Oct;90(1):98-105 - PubMed
  41. Biochemistry. 2008 Feb 12;47(6):1631-9 - PubMed
  42. Science. 2009 Jul 24;325(5939):473-7 - PubMed
  43. Cell. 2006 Jan 27;124(2):263-6 - PubMed
  44. Semin Cancer Biol. 2008 Oct;18(5):349-55 - PubMed
  45. Cell. 2010 Apr 2;141(1):39-51 - PubMed
  46. Pharmacol Ther. 2015 Mar;147:22-31 - PubMed
  47. J Biol Chem. 2014 Apr 4;289(14):10211-22 - PubMed
  48. Nat Cell Biol. 2013 Jun;15(6):647-58 - PubMed
  49. Int J Cancer. 2015 Mar 15;136(6):E602-13 - PubMed

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