Pro- and Antitumorigenic Capacity of Immunoproteasomes in Shaping the Tumor Microenvironment.
Animals
Antineoplastic Agents
/ therapeutic use
Cell Line, Tumor
Colitis
/ pathology
Cysteine Endopeptidases
/ deficiency
Cytokines
/ metabolism
Female
Histocompatibility Antigens Class I
/ metabolism
Humans
Melanoma, Experimental
/ drug therapy
Mice
Mice, Inbred C57BL
Mice, Knockout
Proteasome Endopeptidase Complex
/ genetics
T-Lymphocytes, Cytotoxic
/ immunology
Tumor Microenvironment
/ immunology
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
10
06
2020
revised:
14
12
2020
accepted:
09
03
2021
pubmed:
13
3
2021
medline:
21
1
2022
entrez:
12
3
2021
Statut:
ppublish
Résumé
Apart from the constitutive proteasome, the immunoproteasome that comprises the three proteolytic subunits LMP2, MECL-1, and LMP7 is expressed in most immune cells. In this study, we describe opposing roles for immunoproteasomes in regulating the tumor microenvironment (TME). During chronic inflammation, immunoproteasomes modulated the expression of protumorigenic cytokines and chemokines and enhanced infiltration of innate immune cells, thus triggering the onset of colitis-associated carcinogenesis (CAC) in wild-type mice. Consequently, immunoproteasome-deficient animals (LMP2/MECL-1/LMP7-null mice) were almost completely resistant to CAC development. In patients with ulcerative colitis with high risk for CAC, immunoproteasome-induced protumorigenic mediators were upregulated. In melanoma tumors, the role of immunoproteasomes is relatively unknown. We found that high expression of immunoproteasomes in human melanoma was associated with better prognosis. Similarly, our data revealed that the immunoproteasome has antitumorigenic activity in a mouse model of melanoma. The antitumor immunity against melanoma was compromised in immunoproteasome-deficient mice because of the impaired activity of CD8
Identifiants
pubmed: 33707310
pii: 2326-6066.CIR-20-0492
doi: 10.1158/2326-6066.CIR-20-0492
pmc: PMC8355016
mid: NIHMS1684780
doi:
Substances chimiques
Antineoplastic Agents
0
Cytokines
0
Histocompatibility Antigens Class I
0
LMP-2 protein
144416-78-4
Cysteine Endopeptidases
EC 3.4.22.-
LMP7 protein
EC 3.4.25.1
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
682-692Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139641
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141513
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
Références
EMBO Mol Med. 2014 Feb;6(2):226-38
pubmed: 24399752
Nat Rev Immunol. 2014 May;14(5):329-42
pubmed: 24751956
Cancer Cell. 2004 May;5(5):417-21
pubmed: 15144949
Gut. 2010 Jul;59(7):896-906
pubmed: 20581238
Oncotarget. 2017 Feb 7;8(31):50873-50888
pubmed: 28881611
J Immunol. 2012 Oct 15;189(8):4182-93
pubmed: 22984077
Aliment Pharmacol Ther. 2005 Jan 15;21(2):109-20
pubmed: 15679760
Front Oncol. 2019 Nov 22;9:1283
pubmed: 31824858
Nat Commun. 2020 Feb 14;11(1):896
pubmed: 32060274
Immunity. 2010 Jan 29;32(1):29-40
pubmed: 20045355
Eur J Immunol. 1996 Apr;26(4):863-9
pubmed: 8625980
Trends Immunol. 2016 Nov;37(11):724-737
pubmed: 27614798
Science. 2007 Jun 1;316(5829):1349-53
pubmed: 17540904
Immunol Today. 2000 Jul;21(7):317-9
pubmed: 10950502
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18599-604
pubmed: 20937868
PLoS One. 2012;7(12):e51848
pubmed: 23272179
J Exp Med. 1998 Dec 21;188(12):2357-68
pubmed: 9858522
J Immunol. 2010 Jul 1;185(1):634-41
pubmed: 20525886
Nat Rev Immunol. 2010 Jan;10(1):73-8
pubmed: 20010787
Oncotarget. 2017 Jan 10;8(31):50447-50459
pubmed: 28881574
Nat Rev Mol Cell Biol. 2001 Mar;2(3):179-87
pubmed: 11265247
Nat Immunol. 2011 Dec 25;13(2):129-35
pubmed: 22197977
J Clin Invest. 2006 Dec;116(12):3195-203
pubmed: 17124531
Int J Biochem Cell Biol. 2003 May;35(5):606-16
pubmed: 12672453
Trends Immunol. 2008 Oct;29(10):469-78
pubmed: 18775672
Rev Physiol Biochem Pharmacol. 2003;148:81-104
pubmed: 12687403
Mucosal Immunol. 2014 Sep;7(5):1106-15
pubmed: 24424523
Nat Med. 2009 Jul;15(7):781-7
pubmed: 19525961
Trends Cancer. 2017 Oct;3(10):726-741
pubmed: 28958390
FEBS Lett. 1996 Mar 25;383(1-2):109-13
pubmed: 8612775
Biochim Biophys Acta. 2004 Nov 29;1695(1-3):19-31
pubmed: 15571806
EMBO J. 1998 Dec 15;17(24):7151-60
pubmed: 9857172
Nat Rev Cancer. 2004 May;4(5):349-60
pubmed: 15122206