Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity.
Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity.
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DOI：
10.1038/s41467-022-34665-z
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发表时间：
2022-11-11
影响因子：
16.6
通讯作者：
Xin, Li
中科院分区：
文献类型：
--
作者：
Jia, Deyong;Zhou, Zhicheng;Kwon, Oh-Joon;Zhang, Li;Wei, Xing;Zhang, Yiqun;Yi, Mingyang;Roudier, Martine P.;Regier, Mary C.;Dumpit, Ruth;Nelson, Peter S.;Headley, Mark;True, Lawrence;Lin, Daniel W.;Morrissey, Colm;Creighton, Chad J.;Xin, Li
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. Forkhead transcription factor FoxF2 plays a crucial role in the development of organs derived from primitive gut. Here the authors show that reduction of Foxf2 expression in stromal cells is associated with high grade prostate cancer and that increasing prostatic stromal Foxf2 sensitizes prostate cancer to immune checkpoint blockade.
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影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
8
作者：
Kwon OJ;Zhang L;Jia D;Xin L
通讯作者：
Xin L
影响因子：
4.4
作者：
Gorbachev, Anton V.;Kobayashi, Hirobito;Fairchild, Robert L.
通讯作者：
Fairchild, Robert L.
影响因子：
5.4
作者：
Degl'Innocenti, E;Grioni, M;Bellone, M
通讯作者：
Bellone, M
影响因子：
50.3
作者：
Choi N;Zhang B;Zhang L;Ittmann M;Xin L
通讯作者：
Xin L