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PMID: 19010878 Published · ppublish English Journal Article Review

Transforming growth factor beta: tumor suppressor or promoter? Are host immune cells the answer?

Cancer research ·Vol. 68 ·No. 22 ·2008-11-15 ·Pages 9107-11

Yang L, Moses HL

Abstract

Therapies targeting transforming growth factor beta (TGFbeta) signaling using neutralizing antibodies and small molecular inhibitors are in multiple clinical trails. However, TGFbeta is known to work as both a tumor suppressor and a tumor promoter, and current knowledge does not provide sufficient information on what factors mediate this switch in function and when this switch occurs. Recent advances in multiple disciplines suggest that immune cells from the tumor host may provide the answer.

MeSH Terms
Animals CD11b Antigen/physiology Carcinogens Humans Immune System/physiology Inflammation/etiology Myeloid Cells/physiology Receptors, Chemokine/physiology Signal Transduction/physiology Transforming Growth Factor beta/antagonists & inhibitors,physiology Tumor Suppressor Proteins/physiology
Chemicals
CD11b Antigen Carcinogens Gr-1 protein, mouse Receptors, Chemokine Transforming Growth Factor beta Tumor Suppressor Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Yang Li
Department of Cancer Biology, the Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tenessee 37232, USA. li.yang@vanderbilt.edu
Moses Harold L
References (35)
35 references, click to expand
  1. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner.
    J Exp Med. 2005 Oct 17;202(8):1075-85 PMID: 16230475
  2. Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17.
    Cancer Res. 2008 May 15;68(10):3915-23 PMID: 18483277
  3. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.
    Science. 2006 Sep 29;313(5795):1960-4 PMID: 17008531
  4. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer.
    Nat Med. 2007 Jul;13(7):828-35 PMID: 17603493
  5. Effect of conditional knockout of the type II TGF-beta receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis.
    Cancer Res. 2005 Mar 15;65(6):2296-302 PMID: 15781643
  6. Molecular predictors of survival after adjuvant chemotherapy for colon cancer.
    N Engl J Med. 2001 Apr 19;344(16):1196-206 PMID: 11309634
  7. Stromal fibroblasts in cancer initiation and progression.
    Nature. 2004 Nov 18;432(7015):332-7 PMID: 15549095
  8. Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin.
    Nature. 2007 Apr 5;446(7136):690-4 PMID: 17377533
  9. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells.
    Nature. 2007 Jul 26;448(7152):484-487 PMID: 17581588
  10. Overexpression of transforming growth factor beta1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation.
    Cancer Res. 2004 Jul 1;64(13):4405-10 PMID: 15231647
  11. Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice.
    Cancer Res. 2006 Jan 15;66(2):828-38 PMID: 16424015
  12. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis.
    Nat Cell Biol. 2006 Dec;8(12):1369-75 PMID: 17128264
  13. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4.
    Cell. 2008 Apr 4;133(1):66-77 PMID: 18394990
  14. The dual adverse effects of TGF-beta secretion on tumor progression.
    Cancer Cell. 2005 Nov;8(5):349-50 PMID: 16286241
  15. Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia.
    Cancer Cell. 2007 Oct;12(4):313-27 PMID: 17936557
  16. TGF-beta: a mobile purveyor of immune privilege.
    Immunol Rev. 2006 Oct;213:213-27 PMID: 16972906
  17. Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity.
    Blood. 2008 Apr 15;111(8):4233-44 PMID: 18272812
  18. Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis.
    Cancer Cell. 2008 Jan;13(1):23-35 PMID: 18167337
  19. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells.
    Nat Biotechnol. 2007 Aug;25(8):911-20 PMID: 17664940
  20. Cancer immunology. Cancer's bulwark against immune attack: MDS cells.
    Science. 2008 Jan 11;319(5860):154-6 PMID: 18187637
  21. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer.
    Nat Rev Cancer. 2006 Jul;6(7):506-20 PMID: 16794634
  22. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation.
    J Exp Med. 2005 Oct 3;202(7):919-29 PMID: 16186184
  23. Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation.
    Cancer Res. 2006 Oct 15;66(20):9837-44 PMID: 17047044
  24. Loss of transforming growth factor-beta type II receptor promotes metastatic head-and-neck squamous cell carcinoma.
    Genes Dev. 2006 May 15;20(10):1331-42 PMID: 16702406
  25. Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice.
    Cancer Res. 2002 Nov 15;62(22):6362-6 PMID: 12438215
  26. Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways.
    Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4365-70 PMID: 17360530
  27. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion.
    Nat Genet. 2007 Apr;39(4):467-75 PMID: 17369830
  28. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression.
    Genes Dev. 2006 Nov 15;20(22):3147-60 PMID: 17114585
  29. High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene.
    Cancer Cell. 2007 Feb;11(2):147-60 PMID: 17292826
  30. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis.
    Cancer Cell. 2004 Oct;6(4):409-21 PMID: 15488763
  31. Inhibition of TGFbeta signaling in cancer therapy.
    Curr Opin Genet Dev. 2006 Feb;16(1):30-7 PMID: 16377175
  32. An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments.
    Cancer Res. 2008 May 15;68(10):3835-43 PMID: 18483268
  33. Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence.
    J Exp Med. 2003 Dec 1;198(11):1741-52 PMID: 14657224
  34. A failure of transforming growth factor-beta1 negative regulation maintains sustained NF-kappaB activation in gut inflammation.
    J Biol Chem. 2004 Feb 6;279(6):3925-32 PMID: 14600158
  35. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment.
    Cancer Cell. 2006 Aug;10(2):99-111 PMID: 16904609
Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-08-2556
Email
li.yang@vanderbilt.edu
Published
2008-11-15
Pages
9107-11
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC2741321
Subset
IM
Grants
NCI NIH HHS · R01 CA102162-06A1 · United States
NCI NIH HHS · R01 CA102162 · United States
NCI NIH HHS · U54 CA126505 · United States
NCI NIH HHS · R01 CA085492 · United States
NCI NIH HHS · R01 CA085492-06A1 · United States
NCI NIH HHS · U54 CA126505-030001 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-08-2556 PMC Full Text View journal details
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