Abstract:
: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. Cancer Immunol Res; 6(5); 528-38. ©2018 AACR.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Winerdal ME,Krantz D,Hartana CA,Zirakzadeh AA,Linton L,Bergman EA,Rosenblatt R,Vasko J,Alamdari F,Hansson J,Holmström B,Johansson M,Winerdal M,Marits P,Sherif A,Winqvist Odoi
10.1158/2326-6066.CIR-17-0466subject
Has Abstractpub_date
2018-05-01 00:00:00pages
528-538issue
5eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-17-0466journal_volume
6pub_type
杂志文章abstract::One of the obstacles for cancer immunotherapy is the inefficiency of CD8(+) T-cell recruitment to tumors. STAT3 has been shown to suppress CD8(+) T-cell antitumor functions in various cancer models, in part by restricting accumulation of CD8(+) T cells. However, the underlying molecular mechanism by which STAT3 in CD8...
journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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doi:10.1158/2326-6066.CIR-14-0220-T
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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pub_type: 杂志文章,评审
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更新日期:2014-05-01 00:00:00
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journal_title:Cancer immunology research
pub_type: 杂志文章,多中心研究
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
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journal_title:Cancer immunology research
pub_type: 杂志文章
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