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 those with hormone receptor-positive breast cancer; 34 percent in those with HER2-positive breast cancer; and 46 percent in those with triple-negative breast cancer. 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 the brain. By unraveling the complex interactions between immune cells, the TME, and the bacterial microbiome, this study may pave the way for more effective and personalized treatments for patients with breast cancer brain metastasis.
Progress Thus Far
Dr. Joyce is systematically exploring TME components of breast cancer BrM (BC-BrM), specifically conducting a comprehensive investigation of immune cells found in the TME. She and her colleagues found key characteristics about the immune TME. Specifically, they are focused on immune cells called macrophages that can be recruited to the brain tumor and play a major role in suppressing the anti-tumor immune response and fueling tumor growth. Her team is working to understand how macrophages promote breast cancer brain metastasis and to identify new ways to target them therapeutically. In the last year, they found that combining radiation therapy with a drug that broadly targets macrophages promotes durable tumor control and even long-term remission in certain laboratory models. In another line of study, her team developed the first vascular atlas of brain metastases originating from breast and other cancers. Building on this work, Dr. Joyce and her colleagues discovered that a component of the immune system called the complement pathway is activated within brain metastases and appears to connect macrophages to the tumor’s blood vessels. They have also shown that a specialized population of macrophages that accumulate fat droplets inside tumors, called lipid-associated macrophages, are strongly immunosuppressive.
What’s next
In the next year, the Joyce team will explore the three interconnected lines of study. Following up on their laboratory work with radiation, the team will determine what distinguishes the group of exceptional responders from non-responders, using cutting-edge spatial and single-cell genomic technologies to map the immune landscape of responding tumors. They will also test whether blocking the complement pathway and its effect on the macrophage-blood vessel interaction can slow tumor growth and normalize the vasculature in brain metastases. Building on their work on lipid-associated macrophages, Dr. Joyce’s team will develop a laboratory model to further characterize lipid associated macrophages and identify targets to reverse their immune suppressive activity. Together, Dr. Joyce’s work will address a fundamental gap in our understanding of how the immune environment of brain metastases sustains tumor growth and resists treatment—their results may inform new therapeutic strategies for these patients who currently have limited options.
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 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. Most recently, Dr. Joyce was elected by the European Association for Cancer Research as President for the 2026-28 cycle.
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.
