Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 11 2022
11 11 2022
Historique:
received:
28
12
2021
accepted:
02
11
2022
pubmed:
12
11
2022
medline:
16
11
2022
entrez:
11
11
2022
Statut:
epublish
Résumé
Cancer-associated fibroblasts (CAFs) mediate an immunosuppressive effect, but the underlying mechanism remains incompletely defined. Here we show that increasing prostatic stromal Foxf2 suppresses the growth and progression of both syngeneic and autochthonous mouse prostate cancer models in an immunocompetent context. Mechanistically, Foxf2 moderately attenuates the CAF phenotype and transcriptionally downregulates Cxcl5, which diminish the immunosuppressive myeloid cells and enhance T cell cytotoxicity. Increasing prostatic stromal Foxf2 sensitizes prostate cancer to the immune checkpoint blockade therapies. Augmenting lung stromal Foxf2 also mediates an immunosuppressive milieu and inhibits lung colonization of prostate cancer. FOXF2 is expressed higher in the stroma of human transition zone (TZ) than peripheral zone (PZ) prostate. The stromal FOXF2 expression level in primary prostate cancers inversely correlates with the Gleason grade. Our study establishes Foxf2 as a stromal transcription factor modulating the tumor immune microenvironment and potentially explains why cancers are relatively rare and indolent in the TZ prostate.
Identifiants
pubmed: 36369237
doi: 10.1038/s41467-022-34665-z
pii: 10.1038/s41467-022-34665-z
pmc: PMC9652358
doi:
Substances chimiques
Forkhead Transcription Factors
0
FOXF2 protein, human
0
Foxf2 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6828Subventions
Organisme : NCI NIH HHS
ID : R01 CA271457
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : R01DK107436
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R01CA271457
Informations de copyright
© 2022. The Author(s).
Références
Eur J Immunol. 2005 Jan;35(1):66-75
pubmed: 15597325
Cancer Discov. 2019 Feb;9(2):282-301
pubmed: 30366930
Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11896-903
pubmed: 12909713
Am J Surg Pathol. 1988 Dec;12(12):897-906
pubmed: 3202246
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20611-6
pubmed: 24218555
PLoS Genet. 2016 Jan 08;12(1):e1005769
pubmed: 26745863
Front Cell Dev Biol. 2021 Feb 05;8:604627
pubmed: 33634098
iScience. 2019 Mar 29;13:328-338
pubmed: 30878879
Cancer Cell. 2012 Feb 14;21(2):253-65
pubmed: 22340597
Development. 2006 Mar;133(5):833-43
pubmed: 16439479
Science. 2020 Jul 17;369(6501):
pubmed: 32675345
Prostate. 2009 Oct 1;69(14):1538-47
pubmed: 19562724
Cancer Res. 1997 Aug 15;57(16):3325-30
pubmed: 9269988
J Immunol. 2007 Feb 15;178(4):2278-86
pubmed: 17277133
Cell Rep. 2022 Sep 6;40(10):111313
pubmed: 36070687
BJU Int. 2006 Oct;98(4):886-97
pubmed: 16978289
Am J Pathol. 2011 Jun;178(6):2461-9
pubmed: 21641374
J Urol. 2014 Jan;191(1):60-7
pubmed: 23770146
J Urol. 2019 Mar;201(3):503-509
pubmed: 30316896
Prostate. 2015 Feb;75(2):183-90
pubmed: 25327466
Cancer Res. 2012 Apr 1;72(7):1878-89
pubmed: 22350410
Mol Cell. 2016 Sep 15;63(6):976-89
pubmed: 27594448
RNA. 2008 Nov;14(11):2290-6
pubmed: 18812437
Am J Pathol. 2013 Sep;183(3):758-73
pubmed: 23886891
Dev Dyn. 2000 May;218(1):136-49
pubmed: 10822266
BMC Med Genomics. 2010 Mar 16;3:8
pubmed: 20233430
Cancer Res. 2008 Jun 1;68(11):4331-9
pubmed: 18519693
Cell. 1989 Mar 24;56(6):917-30
pubmed: 2538247
J Cell Physiol. 2007 Jan;210(1):111-21
pubmed: 17044071
Semin Immunol. 2020 Apr;48:101417
pubmed: 33077325
Prostate Cancer Prostatic Dis. 2008;11(2):173-80
pubmed: 17646851
Nat Rev Urol. 2022 Feb;19(2):101-115
pubmed: 34667303
Development. 2001 Jun;128(12):2397-406
pubmed: 11493558
Immunol Cell Biol. 2011 Feb;89(2):207-15
pubmed: 21221121
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Cell Stem Cell. 2019 May 2;24(5):753-768.e6
pubmed: 30982770
Front Immunol. 2019 Aug 02;10:1835
pubmed: 31428105
Oncogene. 2020 Nov;39(48):7142-7151
pubmed: 33009488
BJU Int. 2009 Jun;103(11):1574-80
pubmed: 19220249
Nat Rev Cancer. 2020 Mar;20(3):174-186
pubmed: 31980749
BJU Int. 2004 Dec;94(9):1221-5
pubmed: 15610093
Differentiation. 2008 Jul;76(6):606-23
pubmed: 18494814
Cell Mol Gastroenterol Hepatol. 2020;10(3):581-599
pubmed: 32454112
Dev Cell. 2015 Jul 6;34(1):19-32
pubmed: 26120030
Immunity. 2013 Oct 17;39(4):782-95
pubmed: 24138885
Cell Stem Cell. 2012 Nov 2;11(5):676-88
pubmed: 23122291
J Urol. 1991 Oct;146(4):1069-76
pubmed: 1895423
Trends Immunol. 2016 Mar;37(3):208-220
pubmed: 26858199
Oncogene. 2021 Jan;40(1):203-214
pubmed: 33110232
Toxicol Pathol. 2012;40(1):5-17
pubmed: 22021166
Dis Model Mech. 2018 Apr 19;11(4):
pubmed: 29686035
Immunity. 2018 Mar 20;48(3):399-416
pubmed: 29562192
PLoS One. 2013 Jun 24;8(6):e66855
pubmed: 23826159
Gastroenterology. 2013 May;144(5):1001-11
pubmed: 23376422
Stem Cells. 2020 Nov;38(11):1479-1491
pubmed: 32627901
PLoS Genet. 2017 Aug 10;13(8):e1006951
pubmed: 28797033
J Clin Oncol. 2013 Aug 20;31(24):2991-7
pubmed: 23775960
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8199-206
pubmed: 26720472