During the lecture, Prof. Zitvogel will discuss the association between the gut microbiota and therapeutic effectiveness of alkylating agents, platinum salts, and immune checkpoint inhibitors. Additionally, Prof. Zitvogel will cover the latest findings that support the diagnosis of dysbiosis in patients with cancer and the predictive gut biomarkers of sensitivity or resistance to PD-1 blockade. Finally, she will discuss the potential of developing and applying oncomicrobiotics in cancer therapies to increase/reinstate the immune tone of patients.
A Rewarding Career in Immuno-Oncology
Prof. Zitvogel has dedicated more than 20 years of her career to advancing the field of cancer immunology and immunotherapy. She has authored or co-authored more than 300 publications and was named the First Female Immunologist in Europe in 2013 by Lab Times magazine, based on 7,598 citations for her 111 papers published between 2005 and 2011. Prof. Zitvogel is also a dedicated educator; throughout her career, she has directed the work of 28 graduate students and 39 postdoctoral fellows.
In addition to her professorship at the University of Paris Medical School, Prof. Zitvogel is the director of U1015 INSERM Tumor Immunology and Immunotherapy Laboratory at Institut Gustave Roussy and co-director of the Centre for Clinical Investigation in Biotherapies of Cancer.
Pioneering New Concepts in Cancer Immunology
At Institut Gustave Roussy, Prof. Zitvogel has established a well-recognized research program in tumor immunology and immunotherapy. Her past research accomplishments have served as the foundation for important advances in cancer immunology.
She pioneered the concept of immunogenic cell death—the idea that, depending on the upstream triggers, apoptosis can stimulate the innate immune system to initiate a cognate response against dead-cell antigens. Her team went on to demonstrate that the anticancer activity of radiotherapy, chemotherapy, and tyrosine-kinase inhibitors is mediated, at least in part, by the immune system.
Her work on dendritic cells and innate effectors, such as the natural killer cells and natural killer T cells, has provided important insights about their role in tumor development and exome-based vaccine design. Her team successfully completed two clinical trials, a phase I trial on autologous dendritic cell–derived exomes in patients with stage IV melanoma, and a phase II trial in patients with non–small cell lung cancer using second-generation exomes derived from dendritic cells. This work has shown that exosomes, employed as a therapeutic intervention on the host immune system, may be of therapeutic value.
Her current research interests fall into three main categories: (1) studies of the procancer and anticancer inflammatory and immunological activity of the gut microbiota, (2) the application of monoclonal antibodies in personalized immunotherapy developed based on a patient’s unique tumor microenvironment, and (3) characterization and differentiation of tumor-invading natural killer cells.
Uncovering the Role of Gut Microbiota in Cancer Immunotherapy
Prof. Zitvogel’s latest research has focused on uncovering the role of gut microbiome composition in cancer immunotherapy.1-4 Her team recently revealed that certain constituents of gut microbiota may influence the efficacy and toxicity of cancer immunotherapy during the CTLA-4 checkpoint blockade.1,2 Specifically, Prof. Zitvogel and colleagues demonstrated that the therapeutic efficacy of anti–CTLA-4 antibodies is lost in mice treated with broad-spectrum antibiotics or in mice kept under germ-free conditions.2 This effect was observed in sarcomas, melanomas, and colon cancer. According to Prof. Zitvogel, these findings will likely introduce a new direction in immuno-oncology research focused on finding adjunctive antibiotics that may facilitate the effectiveness of cancer immunotherapy by ensuring optimal microbiome composition.
Prof. Zitvogel has received numerous prestigious recognitions from the French government and French professional associations for her clinical research accomplishments in immuno-oncology. In 2000, she was awarded the Gustave Roussy Prize, followed by the Charles Oberling Prize in 2005 and the Gallet & Breton Prize in 2007. Since 2012, she has been a member of France’s National Academy of Medicine, Biology Division, and a permanent member of the European Academy of Cancer Sciences.