Skip to main content
Article thumbnail
Location of Repository

The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer

By C Horlock, B Stott, P J Dyson, M Morishita, R C Coombes, P Savage and J Stebbing

Abstract

In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (Treg), Th17, natural killer (NK) and NK T (NKT) cells before, during and after trastuzumab therapy was investigated. Sequential frequencies of circulating Treg cells, Th17 cells, NK and NKT cells were measured in peripheral blood of breast cancer patients and normal controls throughout therapy. Individuals with breast cancer had significantly higher Treg frequencies of peripheral blood compared with healthy controls (9.2 or 8.6 vs 6%; P<0.05), and no significant differences in Treg frequencies were observed between HER2-positive and HER2-negative individuals. The number of Th17 cells was lowest in HER2-positive patients compared with both healthy controls and HER2-negative patients (0.31 vs 0.75% or 0.84%; P=0.01). There appeared to be an inverse relationship between Treg and Th17 frequencies in metastatic breast cancer (MBC) with Treg levels significantly reduced during treatment with trastuzumab (P=0.04), whereas Th17 frequencies were concomitantly increased (P=0.04). This study supports earlier data that Treg cells are present at higher frequencies in breast cancer patients compared with healthy individuals. For the first time, we show that HER2-positive individuals with breast carcinomas have reduced numbers of circulating Th17 cells, which appear, in turn to have an inverse relationship with Treg frequency in MBC. The change in balance of the Treg : Th17 ratio appears to characterise the cancer state, and furthermore, is disrupted by trastuzumab therapy

Topics: Translational Therapeutics
Publisher: Nature Publishing Group
OAI identifier: oai:pubmedcentral.nih.gov:2670001
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2007). Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment.
    2. (2007). Differentiation and function of Th17 T cells. Curr Opin Immunol 19: 281–286 Trzonkowski
    3. (2006). IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients.
    4. (2003). Increase of regulatory T cells in the peripheral blood of cancer patients.
    5. (2007). Low density of CD3+, CD4+ and CD8+ cells is associated with increased risk of relapse in squamous cell cervical cancer.
    6. (2002). Med 201: 233–240 Liyanage

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.