EPFL BioE Talks SERIES "Stiffening Cancer Cells Enhances T-Cell Mechanical Force and Anti-Tumor Efficacy"
Event details
| Date | 26.04.2021 |
| Hour | 16:30 › 17:00 |
| Speaker | Prof. Li Tang, Institute of Bioengineering & Institute of Materials, 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 cell softening accompanies malignancy and promotes tumor progression. However, the impact of cancer cell biomechanics on T-cell mediated cytotoxicity and thus the therapeutic outcome of immunotherapy remains elusive. In this talk, I will show that cancer cell softness deriving from the enrichment of endogenous cholesterol in the plasma membrane hampers T-cell mediated killing. Stiffening the cancer cells through cholesterol depletion is an effective biomechanical intervention leading to enhanced cytotoxicity of T-cells and efficacy of adoptive T-cell immunotherapy against solid tumors in multiple models. Stiffening cancer cells has a negligible influence on T-cell receptor signaling and subsequent cytolytic enzyme degranulation (e.g., granzyme B), cytokine secretion (e.g., IFN-γ and TNF-α), or Fas/Fas ligand interaction. Instead, the enhanced cytotoxicity against stiffened cancer cells is mediated by augmented T-cell forces arising from increased F-actin polymerization. Our study reveals a new type of immune checkpoint of mechanical basis, which is distinct from biochemical ones. Therapeutically targeting this mechanical immune checkpoint may improve patients’ response to cancer immunotherapies.
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 Anna Fuller Award (2021), Materials Horizons Emerging Investigator (2020), 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 pandemic, 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 cell softening accompanies malignancy and promotes tumor progression. However, the impact of cancer cell biomechanics on T-cell mediated cytotoxicity and thus the therapeutic outcome of immunotherapy remains elusive. In this talk, I will show that cancer cell softness deriving from the enrichment of endogenous cholesterol in the plasma membrane hampers T-cell mediated killing. Stiffening the cancer cells through cholesterol depletion is an effective biomechanical intervention leading to enhanced cytotoxicity of T-cells and efficacy of adoptive T-cell immunotherapy against solid tumors in multiple models. Stiffening cancer cells has a negligible influence on T-cell receptor signaling and subsequent cytolytic enzyme degranulation (e.g., granzyme B), cytokine secretion (e.g., IFN-γ and TNF-α), or Fas/Fas ligand interaction. Instead, the enhanced cytotoxicity against stiffened cancer cells is mediated by augmented T-cell forces arising from increased F-actin polymerization. Our study reveals a new type of immune checkpoint of mechanical basis, which is distinct from biochemical ones. Therapeutically targeting this mechanical immune checkpoint may improve patients’ response to cancer immunotherapies.
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 Anna Fuller Award (2021), Materials Horizons Emerging Investigator (2020), 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 pandemic, 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
- Prof. Giovanni D'Angelo, EPFL
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD