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 neutrophils, T cells, and macrophages—immune cells found in the TME. They revealed key characteristics about the immune TME: 1) both neutrophils and T cells are enriched within BC-BrM lesions and BC-BrM neutrophils are distinct and more abundant in BrM associated with breast cancer than any other type of brain tumor; 2) the local tumor environment profoundly alters immune cell activity, specifically regarding a subtype of T-cells called tumor-reactive T cells which are lacking in BC-BrM; 3) microglia and macrophages recruited to the brain tumor play a major role in suppressing the anti-tumor immune response. Dr. Joyce and her colleagues also studied how immune cells interact with blood vessels in the brain and identified new molecular pathways that may be driving tumor-associated blood vessel growth. Her work has led to the development of the first vascular atlas of brain metastases originating from melanoma, breast, and lung cancer. In parallel studies, Dr. Joyce’s team explored how the gut microbiome—the bacteria living in the digestive system—can influence brain metastasis. They found that changes in gut bacteria and the metabolites that they produce can delay the onset of brain tumors, pointing to a surprising and important connection between the gut and the brain.
What’s next
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. In the coming year, they will build on recent findings and test new treatment strategies, including therapies that target immune cell function, blood vessel growth, and metabolic pathways in the brain. Their discovery of the link between the microbiome and BC-BrM onset has opened the door for exploration into how altered microbiome metabolism contributes to an immunosuppressive TME. They hope to uncover mechanisms of metabolic reprogramming in BC-BrM that hampers 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 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.
