Display options
Share it on

Front Cell Dev Biol. 2021 May 25;9:658984. doi: 10.3389/fcell.2021.658984. eCollection 2021.

Stromal Cells Underlining the Paths From Autoimmunity, Inflammation to Cancer With Roles Beyond Structural and Nutritional Support.

Frontiers in cell and developmental biology

Amanda M Honan, Zhibin Chen

Affiliations

  1. Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, United States.
  2. Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, United States.

PMID: 34113615 PMCID: PMC8185233 DOI: 10.3389/fcell.2021.658984

Abstract

Stromal cells provide structural support and nutrients in secondary lymphoid organs and non-lymphoid tissues. However, accumulating evidence suggests that a complex relationship exists between stromal cells and immune cells. Interactions between immune cells and stromal cells have been shown to influence the pathology of both autoimmunity and cancer. This review examines the heterogeneity of stromal cells within the lymph node and non-lymphoid tissues during both homeostatic and inflammatory conditions, in particular autoimmunity and cancer, with the goal of better understanding the complex and apparently paradoxical relationship between these two classes of diseases. The review surveys potential novel mechanisms involving the interactions between stromal cells and immune cells which may contribute to the development, pathology and underlying connection between autoimmunity and cancer, including potential pathways from autoimmune inflammation to either "hot" or "cold" tumors. These interactions may provide some insights to explain the rising incidence of both autoimmunity and cancer in young women in industrialized countries and have the potential to be exploited in the development of new interventions for preventions and treatments of both autoimmune diseases and cancer.

Copyright © 2021 Honan and Chen.

Keywords: autoimmunity; cancer; non-lymphoid tissues; secondary lymphoid organs; stromal cells

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):183-9 - PubMed
  2. J Natl Cancer Inst. 1999 Dec 1;91(23):1992-3 - PubMed
  3. J Exp Med. 2018 Jan 2;215(1):35-49 - PubMed
  4. Nat Med. 2003 Jun;9(6):685-93 - PubMed
  5. J Natl Cancer Inst. 2018 Jun 1;110(6):549-550 - PubMed
  6. Methods Mol Biol. 2011;686:49-68 - PubMed
  7. Immunity. 2019 Oct 15;51(4):638-654.e9 - PubMed
  8. Nat Immunol. 2017 Nov;18(11):1218-1227 - PubMed
  9. J Exp Med. 2018 Mar 5;215(3):841-858 - PubMed
  10. J Exp Med. 2010 Apr 12;207(4):689-97 - PubMed
  11. Nat Rev Gastroenterol Hepatol. 2009 Apr;6(4):228-35 - PubMed
  12. Cell Rep. 2020 Mar 24;30(12):4110-4123.e4 - PubMed
  13. Annu Rev Med. 2018 Jan 29;69:301-318 - PubMed
  14. Nat Immunol. 2019 Dec;20(12):1668-1680 - PubMed
  15. Nat Immunol. 2011 Jun;12(6):492-9 - PubMed
  16. Cancer Res. 2013 Apr 1;73(7):2117-26 - PubMed
  17. Front Immunol. 2019 Jan 10;9:3112 - PubMed
  18. FASEB J. 2012 Jul;26(7):2835-46 - PubMed
  19. Cell Death Dis. 2015 Jun 18;6:e1792 - PubMed
  20. Nat Immunol. 2015 Apr;16(4):386-96 - PubMed
  21. Nature. 2005 Feb 24;433(7028):826-33 - PubMed
  22. Immunity. 2019 Mar 19;50(3):707-722.e6 - PubMed
  23. Annu Rev Immunol. 2019 Apr 26;37:457-495 - PubMed
  24. Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10643-8 - PubMed
  25. Immunity. 2018 May 15;48(5):1014-1028.e6 - PubMed
  26. Microsc Res Tech. 1997 Nov 15;39(4):350-64 - PubMed
  27. Biochim Biophys Acta. 2007 Dec;1776(2):160-74 - PubMed
  28. Cell Rep. 2019 Mar 12;26(11):3116-3131.e5 - PubMed
  29. J Immunol. 2012 Mar 1;188(5):2043-5 - PubMed
  30. J Immunol. 2014 Aug 15;193(4):1636-44 - PubMed
  31. Nat Commun. 2016 Jun 21;7:12021 - PubMed
  32. Front Immunol. 2018 Feb 20;9:294 - PubMed
  33. Mucosal Immunol. 2012 May;5(3):232-9 - PubMed
  34. J Natl Cancer Inst. 2018 Jun 1;110(6):608-615 - PubMed
  35. Arthritis Res. 2000;2(5):361-7 - PubMed
  36. Nature. 1988 Nov 3;336(6194):79-81 - PubMed
  37. Nature. 2011 Feb 24;470(7335):548-53 - PubMed
  38. Nat Rev Immunol. 2008 May;8(5):362-71 - PubMed
  39. Nat Rev Cancer. 2006 May;6(5):392-401 - PubMed
  40. PLoS One. 2011;6(11):e27618 - PubMed
  41. J Immunol. 2021 Jan 15;206(2):302-309 - PubMed
  42. Lab Invest. 1996 Feb;74(2):452-66 - PubMed
  43. J Clin Invest. 2018 Jan 2;128(1):16-25 - PubMed
  44. J Exp Med. 2014 Jun 2;211(6):1153-66 - PubMed
  45. Nat Rev Immunol. 2015 Nov;15(11):669-82 - PubMed
  46. Blood. 1996 Jul 15;88(2):667-73 - PubMed
  47. Front Immunol. 2012 Jan 12;2:98 - PubMed
  48. JNCI Cancer Spectr. 2019 Jun 10;3(3):pkz038 - PubMed
  49. Immunity. 2019 Jun 18;50(6):1453-1466.e4 - PubMed
  50. J Immunol. 2007 Feb 1;178(3):1505-11 - PubMed
  51. Nature. 2020 Jul;583(7815):296-302 - PubMed
  52. Med Princ Pract. 2018;27(6):501-507 - PubMed
  53. Nat Immunol. 2014 Jul;15(7):623-30 - PubMed
  54. Immunity. 2005 Mar;22(3):317-28 - PubMed
  55. Immunity. 2019 Jul 16;51(1):119-130.e5 - PubMed
  56. Nat Immunol. 2020 Sep;21(9):974-982 - PubMed
  57. J Clin Oncol. 2005 Sep 1;23(25):6043-53 - PubMed
  58. Nat Immunol. 2013 Mar;14(3):281-9 - PubMed
  59. Nat Immunol. 2019 May;20(5):534-545 - PubMed
  60. J Immunol. 2011 Apr 1;186(7):4147-55 - PubMed
  61. Nat Immunol. 2013 Mar;14(3):271-80 - PubMed
  62. Exp Mol Med. 2020 May;52(5):781-792 - PubMed
  63. J Immunol. 2021 Jan 15;206(2):282-291 - PubMed
  64. Front Immunol. 2014 Mar 18;5:116 - PubMed
  65. Cell Metab. 2019 Mar 5;29(3):576-591 - PubMed
  66. J Exp Med. 2013 Mar 11;210(3):465-73 - PubMed
  67. Immunity. 2019 Sep 17;51(3):561-572.e5 - PubMed
  68. Cell Rep. 2012 Mar 29;1(3):191-9 - PubMed
  69. J Immunol. 2021 Jan 15;206(2):257-263 - PubMed
  70. Nat Commun. 2014 Jun 06;5:3989 - PubMed
  71. Nat Immunol. 2014 Oct;15(10):982-95 - PubMed
  72. Blood. 2011 Dec 1;118(23):6115-22 - PubMed
  73. Front Immunol. 2019 Aug 02;10:1835 - PubMed
  74. Cell. 2010 Mar 19;140(6):871-82 - PubMed
  75. Int Immunol. 2017 Feb 1;29(2):49-58 - PubMed
  76. Annu Rev Immunol. 2015;33:715-45 - PubMed
  77. Front Immunol. 2016 Nov 04;7:480 - PubMed
  78. J Exp Med. 2010 Apr 12;207(4):681-8 - PubMed
  79. Blood. 2012 Dec 6;120(24):4772-82 - PubMed
  80. Front Cardiovasc Med. 2020 Apr 30;7:52 - PubMed
  81. Nat Rev Immunol. 2020 Sep;20(9):566-578 - PubMed
  82. Annu Rev Immunol. 2007;25:649-79 - PubMed
  83. Nat Rev Immunol. 2014 Jul;14(7):495-504 - PubMed
  84. Cell Rep. 2015 Feb 3;10(4):574-85 - PubMed
  85. Mucosal Immunol. 2015 Jan;8(1):141-51 - PubMed
  86. Nature. 1987 Nov 19-25;330(6145):256-9 - PubMed
  87. N Engl J Med. 2018 Jan 11;378(2):158-168 - PubMed
  88. Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6826-E6835 - PubMed
  89. Gastroenterology. 1999 Jul;117(1):49-57 - PubMed
  90. J Clin Invest. 2003 Dec;112(12):1776-84 - PubMed
  91. J Clin Invest. 2018 Jul 2;128(7):2657-2669 - PubMed
  92. Front Immunol. 2020 Jun 26;11:1142 - PubMed
  93. Nature. 2015 Jul 30;523(7562):612-6 - PubMed
  94. Nat Rev Immunol. 2011 Dec 23;12(1):49-60 - PubMed
  95. Nat Immunol. 2020 Jun;21(6):649-659 - PubMed
  96. J Clin Invest. 2007 Mar;117(3):524-9 - PubMed
  97. Nat Rev Gastroenterol Hepatol. 2017 Sep;14(9):510-526 - PubMed
  98. Blood. 2013 May 2;121(18):3768-77 - PubMed
  99. Nat Immunol. 2020 Apr;21(4):369-380 - PubMed
  100. J Exp Med. 2019 Oct 7;216(10):2242-2252 - PubMed
  101. Nat Commun. 2020 Jul 30;11(1):3798 - PubMed
  102. Cell. 2019 Sep 5;178(6):1493-1508.e20 - PubMed
  103. PLoS Biol. 2020 Apr 6;18(4):e3000704 - PubMed
  104. J Immunol. 2021 Jan 15;206(2):292-301 - PubMed
  105. Cancer Res. 1996 Mar 1;56(5):1111-17 - PubMed
  106. J Biol Chem. 2014 Jan 24;289(4):2457-68 - PubMed
  107. CA Cancer J Clin. 2020 Nov;70(6):443-459 - PubMed
  108. Ann Rheum Dis. 1993 Mar;52 Suppl 1:S39-47 - PubMed
  109. World J Gastroenterol. 2016 May 28;22(20):4794-801 - PubMed
  110. Cell. 1988 Oct 21;55(2):301-8 - PubMed
  111. Science. 2002 Nov 15;298(5597):1395-401 - PubMed
  112. Circ Res. 2002 Jun 14;90(11):1189-96 - PubMed
  113. Nature. 2019 Jun;570(7760):246-251 - PubMed
  114. Trends Cancer. 2020 Jul;6(7):605-618 - PubMed
  115. Front Immunol. 2019 May 07;10:1033 - PubMed
  116. Front Immunol. 2019 Apr 16;10:816 - PubMed
  117. Trends Immunol. 2015 Jan;36(1):30-9 - PubMed

Publication Types