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Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity.
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.
Afiliação
  • Jia D; Department of Urology, University of Washington, Seattle, WA, USA.
  • Zhou Z; Department of Urology, University of Washington, Seattle, WA, USA.
  • Kwon OJ; Department of Urology, University of Washington, Seattle, WA, USA.
  • Zhang L; Department of Urology, University of Washington, Seattle, WA, USA.
  • Wei X; Department of Urology, University of Washington, Seattle, WA, USA.
  • Zhang Y; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
  • Yi M; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Roudier MP; Department of Urology, University of Washington, Seattle, WA, USA.
  • Regier MC; Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
  • Dumpit R; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Nelson PS; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Headley M; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • True L; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Lin DW; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Morrissey C; Department of Urology, University of Washington, Seattle, WA, USA.
  • Creighton CJ; Department of Urology, University of Washington, Seattle, WA, USA.
  • Xin L; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Nat Commun ; 13(1): 6828, 2022 11 11.
Article em En | MEDLINE | ID: mdl-36369237
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Neoplasias da Próstata / Fatores de Transcrição Forkhead Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Nat Commun Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Neoplasias da Próstata / Fatores de Transcrição Forkhead Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Nat Commun Ano de publicação: 2022 Tipo de documento: Article