Volume 3 Supplement 1
Towards targeting PD-1/PD-L1 axis in breast cancer, pre-clinical data
© Ghebeh et al. 2015
Published: 14 August 2015
PD-L1 is a ligand that upon binding to its receptor (PD-1) on T-cells leads to T-cell anergy/and or apoptosis [1, 2]. We have shown that PD-L1 is expressed in breast cancer where its expression correlates with estrogen receptor (ER) negativity . To understand the mechanism of the constitutive expression of PD-L1 in tumor cells of ER negative cells we used gene-in and out approach, large scale bioinformatics and immunohistochemistry. We have demonstrated that epithelial to mesenchymal transition (EMT) upregulates PD-L1 expression while cells expressing ER downregulates PD-L1, in parallel with reversal of EMT process. Bioinformatics analysis of gene expression signatures of breast tumors showed a significant correlation between EMT score and PD-L1 mRNA expression. Strikingly, very strong association were found between PD-L1 expression and claudin low breast cancer, a subset of breast cancer known to have high EMT score. In conclusion, we have characterized the expression of PD-L1 in breast cancer and we have demonstrated a strong association between PD-L1 expression, EMT status and claudin-Low breast cancer. Our finding will be essential for choosing the appropriate subset of breast cancer patients that will likely benefit from anti-PD-L1 targeted therapy and understand biological changes upon anti-PD-L1 therapy.
- Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, et al: Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000, 192 (7): 1027-1034. 10.1084/jem.192.7.1027.PubMed CentralView ArticlePubMedGoogle Scholar
- Selenko-Gebauer N, Majdic O, Szekeres A, Hofler G, Guthann E, Korthauer U, Zlabinger G, Steinberger P, Pickl WF, Stockinger H, et al: B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy. J Immunol. 2003, 170 (7): 3637-3644. 10.4049/jimmunol.170.7.3637.View ArticlePubMedGoogle Scholar
- Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G, Elkum N, Alshabanah M, Amer Bin S, Tulbah A, et al: The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia. 2006, 8 (3): 190-198. 10.1593/neo.05733.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.