Journal ArticleDOI
Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells.
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TLDR
It is demonstrated here that T-cell–specific blockade of TGF-β signaling allows the generation of an immune response capable of eradicating tumors in mice challenged with live tumor cells.Abstract:
Despite the existence of tumor-specific antigens and demonstrated presence of tumor-specific immune cells, the majority of tumors manage to avoid immune-mediated destruction. Various mechanisms have been suggested for tumor evasion from immune response. One such mechanism is thought to be mediated by transforming growth factor-beta (TGF-beta), an immunosuppressive cytokine found at the site of most tumors. We demonstrate here that T-cell-specific blockade of TGF-beta signaling allows the generation of an immune response capable of eradicating tumors in mice challenged with live tumor cells. In addition, we provide mechanisms through which abrogation of TGF-beta signaling leads to the enhancement of anti-tumor immunity. Our data indicate that T-cell-specific blockade of TGF-beta signaling has strong therapeutic potential to shift the balance of the immune response in favor of anti-tumor immunity.read more
Citations
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New functions for the matrix metalloproteinases in cancer progression
Mikala Egeblad,Zena Werb +1 more
TL;DR: It is shown that the MMPs have functions other than promotion of invasion, have substrates other than components of the extracellular matrix, and that they function before invasion in the development of cancer.
Journal ArticleDOI
Tumour-educated macrophages promote tumour progression and metastasis
TL;DR: Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process.
Journal ArticleDOI
Transforming growth factor-beta regulation of immune responses.
TL;DR: This review highlights the findings that have advanced the understanding of TGF-beta in the immune system and in disease.
Journal ArticleDOI
Immunosuppressive Strategies that are Mediated by Tumor Cells
TL;DR: Different strategies employed by tumors to thwart immune responses, including tumor-induced impairment of antigen presentation, the activation of negative costimulatory signals, and the elaboration of immunosuppressive factors are discussed.
Journal ArticleDOI
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
Peter M. Siegel,Joan Massagué +1 more
TL;DR: The cytostatic and apoptotic functions of transforming growth factor-β (TGF-β) help restrain the growth of mammalian tissues; loss of these effects leads to hyperproliferative disorders and is common in cancer.
References
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Journal ArticleDOI
Enhancement of antitumor immunity by CTLA-4 blockade.
TL;DR: In vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors, and this rejection resulted in immunity to a secondary exposure to tumor cells, suggesting that blockade of the inhibitory effects of CTLA4 can allow for, and potentiate, effective immune responses against tumor cells.
Journal ArticleDOI
RAG-1-deficient mice have no mature B and T lymphocytes
Peter Mombaerts,John Iacomini,Randall S. Johnson,Karl Herrup,Susumu Tonegawa,Virginia E. Papaioannou +5 more
TL;DR: The introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells is described and it is shown that this mutation either activates or catalyzes the V(D)J recombination reaction of immunoglobulin and T cell receptor genes.
Journal ArticleDOI
REGULATION OF IMMUNE RESPONSES BY TGF-β*
TL;DR: The accumulated knowledge gained through extensive in vitro functional analyses and from in vivo animal models supports the concept that clinical therapies based on modulation of this cytokine represent an important new approach to the treatment of disorders of immune function.
Journal ArticleDOI
Prostate cancer in a transgenic mouse.
Norman M. Greenberg,Francesco J. DeMayo,Milton J. Finegold,Daniel Medina,Wayne D. Tilley,J O Aspinall,Gerald R. Cunha,A A Donjacour,Robert J. Matusik,Jeffrey M. Rosen +9 more
TL;DR: The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.
Journal ArticleDOI
The Central Role of CD4+ T Cells in the Antitumor Immune Response
Kenneth Hung,Robert J. Hayashi,Anne Lafond-Walker,Charles J. Lowenstein,Drew M. Pardoll,Hyam I. Levitsky +5 more
TL;DR: Analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4+ T cells in orchestrating the host response to tumor.
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