EPFL BioE Talks SERIES "Metabolic Immunoengineering of CD8+ T-Cells Using Interleukin-10 for Enhanced Anti-Tumor Immunity"
Event details
| Date | 26.10.2020 |
| Hour | 16:30 › 17:00 |
| Speaker | Prof. Li Tang, Institute of Bioengineering and Institute of Materials Science & Engineering, EPFL, Lausanne (CH) |
| Location | Online |
| Category | Conferences - Seminars |
WEEKLY EPFL BIOE TALKS SERIES
(note that this talk is number two of a double-feature seminar - see details of the first talk here)
Abstract:
Cancer immunotherapy represented by immune checkpoint blockades has achieved remarkable clinical success. However, an outstanding challenge is that a great majority of patients fail to respond to this therapy. This is in part due to the fact that tumour infiltrating lymphocytes (TILs) become exhausted and eventually incapable to control tumour progression. Among exhausted CD8+ TILs, a subpopulation, termed terminally exhausted CD8+ T-cells, have superior cytotoxicity but largely reduced proliferation capacity, and are known to be the direct contributors to the anti-tumour cytotoxicity. However, this subpopulation do not respond to immune checkpoint blockades or most current immunotherapies and are difficult to expand and maintain with their cytotoxicity. Here, we show that a half-life extended interleukin (IL)-10/Fc fusion protein directly expands the terminally exhausted CD8+ TILs and sustains their cytotoxic functions through in vivo metabolic intervention, leading to eradication of established solid tumours and durable cures in a majority of treated mice when combined with adoptive T-cell transfer immunotherapies. We find that IL-10/Fc reprograms the metabolism of CD8+ T-cells by promoting oxidative phosphorylation leading to robust cell proliferation. Our results provide preclinical evidence that IL-10/Fc is a safe and highly effective therapy that acts on a specific subset of CD8+ TILs distinct from those responding to immune checkpoint blockades and thus can complement and potentially synergize with many existing cancer immunotherapies for markedly enhanced efficacy and response rates. We also identify a mechanism of pathway-specific metabolic regulation by which IL-10/Fc could expand CD8+ T-cells upon persistent antigen stimulation providing insight into the crucial role of metabolic profiles in anti-cancer immunity.
Bio:
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 situation, this seminar can be followed via Zoom web-streaming only, following prior one-time registration through the link above.
(note that this talk is number two of a double-feature seminar - see details of the first talk here)
Abstract:
Cancer immunotherapy represented by immune checkpoint blockades has achieved remarkable clinical success. However, an outstanding challenge is that a great majority of patients fail to respond to this therapy. This is in part due to the fact that tumour infiltrating lymphocytes (TILs) become exhausted and eventually incapable to control tumour progression. Among exhausted CD8+ TILs, a subpopulation, termed terminally exhausted CD8+ T-cells, have superior cytotoxicity but largely reduced proliferation capacity, and are known to be the direct contributors to the anti-tumour cytotoxicity. However, this subpopulation do not respond to immune checkpoint blockades or most current immunotherapies and are difficult to expand and maintain with their cytotoxicity. Here, we show that a half-life extended interleukin (IL)-10/Fc fusion protein directly expands the terminally exhausted CD8+ TILs and sustains their cytotoxic functions through in vivo metabolic intervention, leading to eradication of established solid tumours and durable cures in a majority of treated mice when combined with adoptive T-cell transfer immunotherapies. We find that IL-10/Fc reprograms the metabolism of CD8+ T-cells by promoting oxidative phosphorylation leading to robust cell proliferation. Our results provide preclinical evidence that IL-10/Fc is a safe and highly effective therapy that acts on a specific subset of CD8+ TILs distinct from those responding to immune checkpoint blockades and thus can complement and potentially synergize with many existing cancer immunotherapies for markedly enhanced efficacy and response rates. We also identify a mechanism of pathway-specific metabolic regulation by which IL-10/Fc could expand CD8+ T-cells upon persistent antigen stimulation providing insight into the crucial role of metabolic profiles in anti-cancer immunity.
Bio:
- Li Tang received his B.S. in Chemistry from Peking University in China in 2007, and his Ph.D. in Materials Science and Engineering from University of Illinois at Urbana-Champaign, USA, in 2012, under the supervision of Prof. Jianjun Cheng. He was an Irvington Postdoctoral Fellow in the laboratory of Prof. Darrell Irvine at Massachusetts Institute of Technology during 2013-2016. He joined the faculty of Institute of Bioengineering, and Institute of Materials Science & Engineering, at École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, as a Tenure-Track Assistant Professor in 2016. His research focuses on modulating the immune system using smart biomaterials to develop novel vaccines and immunotherapies. Dr. Tang is the recipient of MIT Technology Review’s "Top 35 Innovators under Age 35" list of China region (2020), Biomaterials Science Emerging Investigator (2019), European Research Council (ERC) starting grant (2018), Nano Research Young Innovator Award (NR 45 under 45 in the world) (2018), and Irvington Postdoctoral Fellowship from Cancer Research Institute (2013).
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 situation, this seminar can be followed via Zoom web-streaming only, following prior one-time registration through the link above.
Practical information
- Informed public
- Registration required
Organizer
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD