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  • Winerdal, Malin E.Karolinska Institutet (author)

Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • American Association for Cancer Research (AACR),2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-356079
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-356079URI
  • https://doi.org/10.1158/2326-6066.CIR-17-0466DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-146190URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:138148756URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This discrepancy has partly been attributed to the shear misidentification of Tregs, but also to the inflammatory profile of the tumor. Our aim was to determine whether tumor-infiltrating Forkhead box P3+ (FOXP3+) cells confer a stable Treg phenotype and to investigate putative beneficial Treg functions, focusing on tumor-promoting inflammatory pathways in UBC. Patients (n = 52) with suspected UBC were prospectively included. We show, by using a broad range of analytical approaches, that tumor-infiltrating CD4+FOXP3+ T cells in UBC phenotypically, functionally, and epigenetically represent a true Treg population. At the invasive front of UBC tumors, we found an inverse relationship between Treg frequency and expression of matrix metalloproteinase 2 (MMP2), a key proinvasive factor induced by tumor-promoting inflammation. Correspondingly, a significant, dose-dependent Treg-mediated downregulation of MMP2 protein and mRNA expression was observed in both macrophages and UBC cells. Also, we found that Treg frequency specifically at the invasive front positively correlated with survival. Thus, we identify Treg-mediated suppression of MMP2 in the tumor microenvironment as a mechanism explaining the paradoxical positive prognostic impact of tumor-infiltrating Tregs in UBC.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Krantz, DavidKarolinska Institutet (author)
  • Hartana, Ciputra A.Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden (author)
  • Zirakzadeh, Ali A.Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden,Department of Medicine, Unit of Allergy and Immunology, Karolinska Institutet, Stockholm, Sweden(Swepub:umu)alizih97 (author)
  • Linton, LudvigKarolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden (author)
  • Bergman, Emma A.Karolinska Institutet (author)
  • Rosenblatt, RobertUmeå universitet,Urologi och andrologi,Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden,Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden; Karolinska Inst, Stockholm South Gen Hosp, Dept Urol, Stockholm, Sweden(Swepub:umu)roro0025 (author)
  • Vasko, JanosUmeå universitet,Patologi,Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden(Swepub:umu)jasvao04 (author)
  • Alamdari, FarhoodVastmanland Hosp, Dept Urol, Vasteras, Sweden (author)
  • Hansson, Johan,1964-Uppsala universitet,Centrum för klinisk forskning, Gävleborg(Swepub:uu)johan031 (author)
  • Holmström, BennyUppsala universitet,Urologkirurgi (author)
  • Johansson, MarkusSundsvall Hosp, Dept Urol, Sundsvall, Sweden (author)
  • Winerdal, MaxKarolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden (author)
  • Marits, PerKarolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden (author)
  • Sherif, AmirUmeå universitet,Urologi och andrologi,Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden(Swepub:umu)amsh0008 (author)
  • Winqvist, OlaKarolinska Institutet (author)
  • Karolinska InstitutetKarolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden (creator_code:org_t)

Related titles

  • In:CANCER IMMUNOLOGY RESEARCH: American Association for Cancer Research (AACR)6:5, s. 528-5382326-60662326-6074

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