MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: Potential implications for immune based therapy of human solid tumors Academic Article uri icon

Overview

MeSH Major

  • Antigens, CD
  • MicroRNAs
  • Neoplasms
  • Receptors, Immunologic

abstract

  • B7-H3, a surface immunomodulatory glycoprotein, inhibits natural killer cells and T cells. The monoclonal antibody (mAb) 8H9 is specific for 4Ig-B7-H3, the long and principal form of B7-H3. Early results from radioimmunotherapy using 8H9 have shown promise in patients with metastatic solid tumors to the central nervous system. Whereas B7-H3 transcript was ubiquitously expressed in a wide spectrum of human solid tumors as well as human normal tissues, B7-H3 protein was preferentially expressed only in tumor tissues. By quantitative reverse transcription-PCR, all three isoforms of microRNA miR-29 (a, b, and c) were highly expressed in normal tissues. However, they were down-regulated in a broad spectrum of solid tumors, including neuroblastoma, sarcomas, brain tumors, and tumor cell lines. B7-H3 protein expression was inversely correlated with miR-29 levels in both cell lines and tumor tissues tested. Using luciferase reporter assay, miR-29a was shown to directly target B7-H3 3' untranslated region, and knock-in and knockdown of miR-29a led to down-regulation and up-regulation, respectively, of B7-H3 protein expression. The ability of miR-29 to control B7-H3 protein expression has implications in immune escape by solid tumors. Differential modulation of this key immunoinhibitory molecule in tumor versus normal tissues may advance both cell-mediated immunotherapy and antibody-based targeted strategies using the B7-H3-specific mAb 8H9.

publication date

  • August 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2719680

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-08-4517

PubMed ID

  • 19584290

Additional Document Info

start page

  • 6275

end page

  • 81

volume

  • 69

number

  • 15