- Open Access
Is immune checkpoint modulation a potential therapeutic option in triple negative breast cancer?
© Klinke; licensee BioMed Central Ltd. 2014
- Published: 7 November 2014
- Breast Cancer
- Epidermal Growth Factor Receptor
- Natural Killer Cell
- Programme Cell Death
The emergence of molecular targeted therapies has revolutionized the clinical treatment of breast cancer. To guide treatment, patient samples are screened for expression of hormone receptors for estrogen and progesterone and the epidermal growth factor receptor HER2. Patients with tumors that do not express any of these three receptors (that is, triple-negative breast cancer) exhibit a worse outcome . Sequencing of cancer genomes suggests that over-expressing an oncogene or eliminating a tumor suppressor gene is also associated with passenger mutations. The presence of these passenger mutations may provide a collective signature that distinguishes malignant from normal cells. Conceptually, the adaptive immune system recognizes cells that present a different antigenic signature and provides a mechanism to control for malignant transformation. One approach to enhance anti-tumor immunity is to increase the number of T cells, either systemically, through inhibiting the action of CTLA-4, or locally, through inhibiting the programmed cell death 1 pathway. Therapeutic inhibition of these pathways is called immune checkpoint modulation . The clinical benefit received by a subset of patients with metastatic melanoma demonstrates proof-of-principle for this therapeutic approach .
DJK conceived the study, performed the bioinformatic analysis, analyzed the experimental data, and wrote the manuscript.
This work was supported by grants from the National Science Foundation (CAREER 1053490) and the National Cancer Institute (NCI) R15CA123123. The content is solely the responsibility of the author and does not necessarily represent the official views of the NCI, the National Institutes of Health, or the National Science Foundation.
- Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007, 13: 4429-4434. 10.1158/1078-0432.CCR-06-3045.View ArticlePubMedGoogle Scholar
- Topalian SL, Drake CG, Pardoll DM: Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012, 24: 207-212. 10.1016/j.coi.2011.12.009.View ArticlePubMedPubMed CentralGoogle Scholar
- Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010, 363: 711-723. 10.1056/NEJMoa1003466.View ArticlePubMedPubMed CentralGoogle Scholar
- Klinke DJ: Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity: a retrospective study. PLoS Comput Biol. 2014, 10: e1003409-10.1371/journal.pcbi.1003409.View ArticlePubMedGoogle Scholar
- Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL: In situ Tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res. 2014, 20: 2773-2782. 10.1158/1078-0432.CCR-13-2702.View 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 credited. 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.