Institut Jules Bordet Brussels, Belgium
Head of the Translational Breast Cancer Laboratory Free University of Brussels
Delineating the heterogeneity of breast cancer cells and assessing how tumor heterogeneity impacts treatment response and clinical outcome.
Triple-negative breast cancer (TNBC) represents 15 to 20 percent of all breast cancers and is defined by the lack of three common breast cancer markers, estrogen and progesterone receptors, as well as HER2. TNBC has the worst outcomes of all breast cancer subtypes with limited treatment options. Although the use of immune checkpoint blockade combined with chemotherapy has been shown to improve the clinical outcome of some of these patients, a significant proportion of patients do not benefit. One reason for the variation in treatment response has to do with the diversity of cell types in and around the tumor (called intra-tumor heterogeneity). Dr. Sotiriou’s research is aimed at assessing the impact of intra-tumor heterogeneity, as well as the tumor-immune microenvironment on treatment response and ultimately patient outcome. These studies will inform better risk assessment and decision making in the treatment of patients with TNBC.
Dr. Sotiriou’s research builds on his previous BCRF-supported work, which utilized cutting edge technologies to interrogate the genomic and cellular heterogeneity in HER2-positive breast cancer. He and his team are extending this technology to assess the impact of tumor and immune cell heterogeneity on response to immunotherapy in TNBC. The team is combining multiple layers of single-cell analyses of tumor tissue from before treatment, at the start of treatment, and from residual disease at the time of surgery to build a complete picture of treatment response. They looked at 37 patients receiving different types of treatment—some got chemotherapy alone while others got a combination of chemotherapy and immunotherapy. They found that the makeup of immune cells, particularly T cells, changed during treatment, and this change differed between the groups receiving chemotherapy vs. chemotherapy and immunotherapy. The team also identified specific types of T cells that seemed to be linked with better responses to chemotherapy. Tumor profiling identified different gene expression patterns that might explain why some tumors resist treatment. Overall, the study gives us a better understanding of how the immune system responds to treatment and may ultimately enable tailored care to spare patients unnecessary side effects related to immunotherapy.
Dr. Sotiriou and his team will continue to study TNBC tumors and the surrounding microenvironment at the single-cell level before treatment and after surgery. They aim to study more samples from patients who were treated with immunotherapy to better evaluate the response to therapy in that group. The team will continue analyses of types of immune cells in the tumor samples, and correlate gene and RNA variance with response to therapy.
Christos Sotiriou, MD, PhD earned a medical degree from the Université Libre de Bruxelles, Belgium, in 1993. He did his internal medicine/oncology residency at the Institut Jules Bordet and earned his specialty in this field in July 1999. From October 1999 through September 2001, he worked as basic research fellow, at the Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. After having completed a PhD Thesis at the Université Libre de Bruxelles in September 2004, he became “Chercheur Qualifié” (Research Faculty Member – tenured position) at the National Foundation for Scientific Research (FNRS, Belgium) in 2005. In March 2010, he took over the lead of the Breast Cancer Translational Research Laboratory J-C Heuson. In October 2013, he was appointed “Maître de Recherche” (Senior Research Associate – tenured position) by the National Foundation for Scientific Research (FNRS, Belgium), and also one of the “Chefs de Clinique” (Heads of clinic) at the Medical Oncology Clinic of the Institut Jules Bordet.
Dr. Sotiriou is a full member of ASCO, AACR, and ESMO, an Elected Member of the Scientific Council of the International Agency for Research on Cancer (World Health Organisation (2012 – 2016), and an Elected Fellow of the European Academy of Cancer Sciences (since 2010), which is hosted under the auspices of European CanCer Organization (ECCO). He is also Advisory Council Member of the Susan G. Komen for the Cure (since June 2010).
Dr. Sotiriou is reviewer for several high impact peer-reviewed journals. He has been elected associated editor of the Annals of Oncology Journal (Breast tumors) (January 2014-December 2015). Internationally renowned researcher, author, and co-author of over 160 peer-reviewed articles, Dr. Sotiriou is focusing his research on genomics in breast cancer.
2005
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