Tumor microenvironment

Our lab investigates the microenvironment in which a tumor arises and the critical influence that non-cancerous stromal and immune cells can have on tumor progression, metastasis and response to therapy.  We analyse both positive and negative signals provided by the normal tissue stroma to the cancer cells, and explore how the microenvironment can be educated by the cancer cells to produce a variety of factors that enhance tumor malignancy.

We are currently focusing much of our efforts on understanding and therapeutically targeting brain malignancies and metastatic disease, both from the perspective of the tumor microenvironment (TME).  Glioblastomas and brain metastases are among the most lethal of cancers, with an average lifespan of a year or less following diagnosis.  Given this dismal patient prognosis, we became very interested in studying these particular brain malignancies several years ago.  We have been fortunate to make several important insights into the brain TME from our recent studies (e.g. Quail et al, Science 2016; Pyonteck et al, Nature Medicine 2013). However, we have much more to discover in terms of elucidating mechanisms of immune suppression, determining how distinct molecular subtypes or genetic drivers in cancer cells may differentially sculpt the brain TME, and exploring how the brain TME is affected by both standard of care therapy and new investigational therapies, including immunotherapies.

In parallel, we continue to explore the entire metastatic process in the context of breast cancer, leading on from our recent findings (Quail et al, Sevenich et al, Nature Cell Biology 2017; Sevenich et al, Nature Cell Biology 2014). 

Our rationale for focusing on these specific diseases comes from the evident challenges in treating brain tumors, our relative paucity of knowledge of the brain TME compared to other organ sites, and from the fact that ~90% of patient deaths result from metastases.

Visit http://joycelab.org for more information.

1. Quail DF, Olson OC, Bhardwaj P, Walsh LA, Akkari L, Quick M, Chen IC, Wendel N, Ben-Chetrit N, Walker J, Holt PR, Dannenberg AJ and Joyce JA (2017). Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis via IL5 and GM-CSF.  Nature Cell Biology 19: 974- 987.
2. Quail DF, Bowman RL, Akkari L, Quick ML, Schuhmacher AJ, Huse JT, Holland EC, Sutton JC and Joyce JA (2016). The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 352: aad3018.
3. Bowman RL, Klemm F, Akkari L, Pyonteck SM, Sevenich L, Quail DF, Dhara S, Simpson K, Gardner EE, Iacobuzio-Donahue C, Brennan CW, Tabar V, Gutin PH and Joyce JA (2016). Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Reports 17: 2445-2459.
4. Sevenich L, Bowman R, Mason SD, Quail DF, Rapaport F, Elie BT, Brogi E Brastianos P, Hahn WC, Holsinger L, Massague J, Leslie CS and Joyce JA (2014). Analysis of tumour and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S. Nature Cell Biology 16: 876-888.
5. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail D, Olson OC, Quick M, Huse J, Teijeiro V, Setty M, Leslie C, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D and Joyce JA (2013). CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nature Medicine 19: 1264-1272.

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• Swiss Bridge
• Swiss Cancer League
• Breast Cancer Research Foundation
• Cancer Research UK
• US National Cancer Institute
• Human Frontiers Science Program
• AIRC/ Marie Curie
• European Molecular Biology Organisation
• Breast Cancer Research Foundation
• Cancer Research UK