Immune-phenotyping and transcriptomic profiling of peripheral blood mononuclear cells from patients with breast cancer: identification of a 3 gene signature which predicts relapse of triple negative breast cancer

Foulds, G.A., Vadakekolathu, J., Abdel-Fatah, T.M.A., Nagarajan, D., Reeder, S., Johnson, C., Hood, S., Moseley, P.M., Chan, S.Y.T., Pockley, A.G. ORCID: 0000-0001-9593-6431, Rutella, S. ORCID: 0000-0003-1970-7375 and McArdle, S.E.B. ORCID: 0000-0001-6929-9782, 2018. Immune-phenotyping and transcriptomic profiling of peripheral blood mononuclear cells from patients with breast cancer: identification of a 3 gene signature which predicts relapse of triple negative breast cancer. Frontiers in Immunology, 9: 2028. ISSN 1664-3224

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Abstract

Background: Interactions between the immune system and tumors are highly reciprocal in nature, leading to speculation that tumor recurrence or therapeutic resistance could be influenced or predicted by immune events that manifest locally, but can be detected systemically.

Methods: Multi-parameter flow cytometry was used to examine the percentage and phenotype of natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), monocyte subsets and regulatory T (Treg) cells in the peripheral blood of of 85 patients with breast cancer (50 of whom were assessed before and after one cycle of anthracycline-based chemotherapy), and 23 controls. Transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) in 23 patients were generated using a NanoString gene profiling platform.

Results: An increased percentage of immunosuppressive cells such as granulocytic MDSCs, intermediate CD14++CD16+ monocytes and CD127negCD25highFoxP3+ Treg cells was observed in patients with breast cancer, especially patients with stage 3 and 4 disease, regardless of ER status. Following neoadjuvant chemotherapy, B cell numbers decreased significantly, whereas monocyte numbers increased. Although chemotherapy had no effect on the percentage of Treg, MDSC and NK cells, the expression of inhibitory receptors CD85j, LIAR and NKG2A and activating receptors NKp30 and NKp44 on NK cells increased, concomitant with a decreased expression of NKp46 and DNAM-1 activating receptors. Transcriptomic profiling revealed a distinct group of 3 patients in the triple negative breast cancer (TNBC) cohort who expressed high levels of mRNA encoding genes predominantly involved in inflammation. The analysis of a large transcriptomic dataset derived from the tumors of patients with TNBC revealed that the expression of CD163, CXCR4, THBS1 predicted relapse-free survival.

Conclusions: The peripheral blood immunome of patients with breast cancer is influenced by the presence and stage of cancer, but not by molecular subtypes. Furthermore, immune profiling coupled with transcriptomic analyses of peripheral blood cells may identify patients with TNBC that are at risk of relapse after chemotherapy.

Item Type: Journal article
Publication Title: Frontiers in Immunology
Creators: Foulds, G.A., Vadakekolathu, J., Abdel-Fatah, T.M.A., Nagarajan, D., Reeder, S., Johnson, C., Hood, S., Moseley, P.M., Chan, S.Y.T., Pockley, A.G., Rutella, S. and McArdle, S.E.B.
Publisher: Frontiers Research Foundation
Date: 11 September 2018
Volume: 9
ISSN: 1664-3224
Identifiers:
NumberType
10.3389/fimmu.2018.02028DOI
Rights: Copyright © 2018 Foulds, Vadakekolathu, Abdel-Fatah, Nagarajan, Reeder, Johnson, Hood, Moseley, Chan, Pockley, Rutella and McArdle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 11 Sep 2018 08:32
Last Modified: 11 Sep 2018 08:32
URI: http://irep.ntu.ac.uk/id/eprint/34466

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