Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer

J Hematol Oncol. 2018 Feb 20;11(1):24. doi: 10.1186/s13045-018-0570-z.

Abstract

GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking receptor for latent transforming growth factor-β (TGF-β) that is abundantly expressed on regulatory T lymphocytes and platelets. GARP regulates the availability of membrane-bound latent TGF-β and modulates its activation. For this reason, GARP expression on immune and non-immune cells is involved in maintaining peripheral tolerance. It plays an important role in preventing inflammatory diseases such as allergy and graft versus host disease (GvHD). GARP is also frequently hijacked by cancer cells to promote oncogenesis. This review summarizes the most important features of GARP biology described to date including gene regulation, protein expression and mechanism in activating latent TGF-β, and the function of GARP in regulatory T cell biology and peripheral tolerance, as well as GARP's increasingly recognized roles in platelet-mediated cancer immune evasion. The promise for GARP-targeted strategy as a novel immunotherapy of cancer is also highlighted.

Keywords: Cancer; GARP; Immune tolerance; Platelets; TGF-β; Treg.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / immunology
  • Blood Platelets / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immune Tolerance
  • Inflammation / complications
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / pathology
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Neoplasms / complications
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / immunology*

Substances

  • LRRC32 protein, human
  • Membrane Proteins
  • Transforming Growth Factor beta