Titles and Affiliations

Professor, Department of Oncology
Ludwig Institute for Cancer Research
Executive Director, Agora Cancer Centre

Research area

Understanding the role of immune cells in mediating breast cancer progression, metastasis, and therapeutic response.

Impact

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 advanced 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 and hopes to exploit her findings to develop novel strategies for treating patients.  

Progress Thus Far

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 the immune cell population in BC-BrM, greater than in any other type of brain tumor. Experiments are underway to understand the mechanisms involved and how they can be harnessed to improve treatment outcomes for breast cancer patients. Following up on these findings, 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. In the last year, they focused on 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. Dr. Joyce discovered that the tumor microbiome promotes early phases of BC-BrM formation. And decreases in components of the normal microbiome impacted the physiology of the healthy brain, creating an environment more suitable for BrM formation. 

What's next

In the coming year, they will continue to investigate the unique changes that immune cells undergo as they enter the brain tumor microenvironment as well as explore other potential immune suppressive processes that occur within the BC-BrM TME. Utilizing state-of-the-art single cell analysis methods, Dr. Joyce and her colleagues will examine T-cell populations in primary breast cancer and matching brain metastases. 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.  

Biography

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.

BCRF Investigator Since

2009