University of Lausanne Lausanne, Switzerland
Professor, Department of Oncology Ludwig Institute for Cancer Research Executive Director, Agora Cancer Centre
Understanding the role of immune cells in mediating breast cancer progression, metastasis, and therapeutic response.
Breast cancer is one of three cancer types that frequently give rise to brain metastases (BrM). Depending on the subtype, a substantial proportion of patients are at high risk of developing BrM over the course of their disease: approximately 14 percent in hormone receptor-positive patients; 34 percent in HER2-positive patients; and 46 percent in triple-negative patients. Unfortunately, the development of BrM confers a devastating prognosis for patients since there are limited treatment strategies for breast cancers that have spread to the brain. Dr. Joyce is investigating the role of the tumor microenvironment (TME) in the progression of breast cancer to BrM. By unraveling the complex interactions between immune cells, the TME, and the bacterial microbiome, this study aims to pave the way for more effective and personalized treatments for patients with breast cancer brain metastasis.
Dr. Joyce is systematically exploring the key TME components of breast cancer BrM (BC-BrM). To date, her team has conducted a comprehensive investigation of neutrophils and T cells—immune cells found in the TME. They found that both neutrophils and T cells are enriched within BC-BrM lesions and that BC-BrM neutrophils have distinct characteristics and are more abundant in BrM associated with breast cancer than any other type of brain tumor. In other studies, they compared the immune cells—macrophages, T cells, and neutrophils— in BC-BrM, to those in normal tissue. They found that the local tumor environment profoundly alters immune cell activity, specifically regarding a subtype of T-cells called tumor-reactive T cells: These T-cells are lacking in BC-BrM, which may explain the resistance of BC-BrM to immunotherapies such as anti-PD1 blockade treatment. In the last year, Dr. Joyce and her colleagues have identified important differences between tumor-reactive T cells in the TME of BC-BrM compared to lung cancer-BrM. Their work also revealed critical functions for neutrophils, which are particularly abundant in BC-BrM. Her team also developed the first vascular atlas of brain metastases originating from melanoma, breast and lung cancer. Experiments are underway to understand the mechanisms involved and how they can be harnessed to improve treatment outcomes for breast cancer patients.
Utilizing state-of-the-art single cell analysis methods, Dr. Joyce and her colleagues will further dissect the spatial relationship between T cells and other immune cells in BC-BrM. They will also utilize laboratory models to investigate the immune-suppressive functions of myeloid cells in BC-BrM tumors and explore the role of the bacterial microbiome in BC-BrM. They hope to decipher the key mechanisms that hamper T cell recruitment, activation, and sustained anti-tumor activity in BC-BrM and provide valuable insights into why these tumors respond poorly to standard-of-care treatment, including immunotherapies.
Johanna A. Joyce, PhD joined the Ludwig Institute of Cancer Research, University of Lausanne, Switzerland in 2016. Prior to that, she led a lab at Memorial Sloan Kettering Cancer Center, New York, USA for 11 years where she was promoted through the ranks to tenured Professor and Full Member. Dr. Joyce has received multiple awards and honors including from the American Cancer Society, the Rita Allen Foundation, the Sidney Kimmel Foundation, the Geoffrey Beene Foundation, and the V Foundation, among others.
The Joyce lab is focused on investigating the tumor microenvironment of primary cancers and metastatic disease, and in determining the critical influence that non-cancerous stromal cells can have on tumor progression and therapeutic response. She received her doctorate in Biology from the University of Cambridge, England in 1999 and completed her postdoctoral training in Dr. Douglas Hanahan’s lab at University of California, San Francisco.
2009
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