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Updated: Mar 11, 2026

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Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer

Alessandra Metelli1, Bill X Wu1, Caroline W Fugle1

  • 1Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.

Cancer Research
|December 4, 2016
PubMed

Insights

The Glycoprotein-A repetitions dominant (GARP) receptor promotes cancer by activating TGFβ, fostering immune tolerance. Targeting GARP with antibodies may limit cancer progression and metastasis.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The Lrrc32 gene encodes GARP, a receptor for latent TGFβ found on platelets and regulatory T cells (Tregs).
  • While Lrrc32 is amplified in breast cancer, GARP's role in cancer remains largely unexplored.

Purpose of the Study:

  • To investigate the expression and function of GARP in various cancers.
  • To elucidate the oncogenic mechanisms of the GARP-TGFβ axis in the tumor microenvironment.

Main Methods:

  • Analysis of GARP expression in human breast, lung, and colon cancers.
  • Genetic studies in epithelial and carcinoma cells in immunodeficient and immunocompetent mice models.
  • Assessment of GARP-specific monoclonal antibody (mAb) efficacy in limiting metastasis.

Main Results:

  • Aberrant GARP expression was observed in human breast, lung, and colon cancers.
  • GARP enhanced TGFβ bioactivity, promoting malignant transformation and Treg activity, thereby driving cancer progression and metastasis.
  • A GARP-specific mAb effectively limited metastasis in a human breast cancer model.

Conclusions:

  • GARP exhibits oncogenic properties by promoting immune tolerance via the TGFβ pathway in the tumor microenvironment.
  • The GARP-TGFβ axis represents a potential therapeutic target for cancer treatment.
  • GARP's role suggests possibilities for novel diagnostic and therapeutic strategies.

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