Johanna A. Joyce

Johanna Joyce is a Professor in the Department of Oncology at the University of Lausanne and Director of the Ludwig Cancer Research Lausanne Branch. She is internationally recognized as a leading authority on the tumor microenvironment (TME), with particular expertise in how non-malignant stromal cells — especially macrophages and other myeloid cells — are co-opted by cancer cells to support tumor growth, angiogenesis, invasion, and immune evasion. Joyce trained at the Cancer Research UK London Research Institute with Martin Raff and subsequently as a fellow with Douglas Hanahan at UCSF, where she began work on cathepsin cysteine proteases in the tumor microenvironment. Using the RIP-Tag model of pancreatic islet carcinogenesis, she demonstrated that cathepsins B and L are upregulated specifically in tumor-associated macrophages during tumor progression, and that their pharmacological inhibition dramatically suppressed tumor growth — revealing stromal cells as unexpected but critical effector compartments for protease-driven tumor progression. At MSKCC (where she led her own lab before moving to Lausanne), Joyce's laboratory pioneered the systematic characterization of tumor microenvironments across brain tumor subtypes, revealing the cellular composition, transcriptional programs, and spatial organization of tumor-associated macrophages (TAMs) and microglia in glioblastoma, medulloblastoma, and brain metastases from other cancers. Her work on glioblastoma — the most aggressive primary brain tumor with median survival under 15 months — has been particularly impactful. She demonstrated that TAMs constitute 30–50% of the glioblastoma tumor mass and are profoundly immunosuppressive through secretion of IL-10, TGF-β, and other factors, as well as expression of immune checkpoints. Her laboratory developed strategies to reprogram TAMs from immunosuppressive M2-like states to pro-inflammatory M1-like states, and showed that targeting CSF1R (which controls TAM survival and identity) can dramatically reduce TAM density and improve survival in glioblastoma mouse models. Joyce's laboratory has also characterized the distinct myeloid microenvironments of brain metastases from different primary tumors (breast cancer, lung cancer, melanoma), revealing how organ-specific myeloid programming shapes the permissiveness of the brain as a metastatic site.

Johanna Joyce 是洛桑大学肿瘤学系教授和路德维希癌症研究洛桑分部主任，是肿瘤微环境（TME）领域的国际公认权威，尤其专注于巨噬细胞和髓样细胞如何被癌细胞劫持以支持肿瘤生长和免疫逃逸。 在使用RIP-Tag模型研究胰腺胰岛癌发生时，她证明了组织蛋白酶B和L特异性在肿瘤相关巨噬细胞中上调，其药理学抑制可显著抑制肿瘤生长。她关于胶质母细胞瘤的研究表明，TAM构成肿瘤质量的30-50%并具有深度免疫抑制性，并开发了将TAM从免疫抑制状态重编程为促炎状态的策略，在胶质母细胞瘤小鼠模型中显著改善了存活率。