Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Nature communications - 13(2022), 1 vom: 11. Nov., Seite 6828 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jia, Deyong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
FOXF2 protein, human |
|---|
| Anmerkungen: |
Date Completed 17.11.2022 Date Revised 23.03.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-022-34665-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM348827946 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM348827946 | ||
| 003 | DE-627 | ||
| 005 | 20231226041204.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-022-34665-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1162.xml |
| 035 | |a (DE-627)NLM348827946 | ||
| 035 | |a (NLM)36369237 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jia, Deyong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.11.2022 | ||
| 500 | |a Date Revised 23.03.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Forkhead Transcription Factors |2 NLM | |
| 650 | 7 | |a FOXF2 protein, human |2 NLM | |
| 650 | 7 | |a Foxf2 protein, mouse |2 NLM | |
| 700 | 1 | |a Zhou, Zhicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Kwon, Oh-Joon |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yiqun |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Mingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Roudier, Martine P |e verfasserin |4 aut | |
| 700 | 1 | |a Regier, Mary C |e verfasserin |4 aut | |
| 700 | 1 | |a Dumpit, Ruth |e verfasserin |4 aut | |
| 700 | 1 | |a Nelson, Peter S |e verfasserin |4 aut | |
| 700 | 1 | |a Headley, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a True, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Daniel W |e verfasserin |4 aut | |
| 700 | 1 | |a Morrissey, Colm |e verfasserin |4 aut | |
| 700 | 1 | |a Creighton, Chad J |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Li |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 13(2022), 1 vom: 11. Nov., Seite 6828 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g number:1 |g day:11 |g month:11 |g pages:6828 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-022-34665-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 |e 1 |b 11 |c 11 |h 6828 | ||