Ep. 84: “T Cells in Inflammation and Cancer” Featuring Dr. Jeffrey Rathmell
Jul 30, 2024
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Dr. Jeffrey Rathmell, the Cornelius Vanderbilt Professor of Immunobiology, dives into T cell metabolism and its critical role in cancer. He discusses how T cells utilize fatty acids as fuel and the intriguing 'obesity paradox' in cancer immunotherapy. Rathmell also reflects on the joys of being a scientist and professor, emphasizing the importance of mentorship and collaboration in research. Explore the metabolic shifts in T cells and their implications for therapy as he shares insights into the evolving landscape of immunology.
T-cell metabolism is pivotal in their immune response, as they adapt their fuel sources based on activation and environmental cues.
Blocking IL-11 signaling has significant implications for extending lifespan and alleviating chronic inflammation-related health issues in mammals.
The use of humanized mouse models enhances our understanding of human immune responses, bridging the gap between animal studies and potential therapies.
Deep dives
Immunometabolism in Cancer Research
Research on the metabolic requirements of T-cells reveals their reliance on specific nutrients to function effectively in the immune response. T-cells alter their metabolism upon activation, switching from a primarily catabolic state to an anabolic state to support growth, proliferation, and the production of antibodies. This dynamic metabolic adaptation has shown that T-cells can utilize a variety of fuels based on their current state and environment, which underscores the intricate relationship between metabolism and immune function. Understanding these metabolic pathways offers potential strategies for targeting T-cell responses, particularly in cancer immunotherapy.
Inhibition of IL-11 and Longevity
A significant study demonstrates that blocking IL-11 signaling can extend the lifespan of mammals, revealing its role in age-related inflammation. IL-11 is associated with chronic inflammation and various age-related health issues, contributing to metabolic syndromes and tissue dysfunction. The research shows that animals treated with IL-11 receptor inhibitors exhibited not only increased longevity but also improved metabolic health without the risk of heightened tumor development. This highlights the potential therapeutic benefits of targeting IL-11 pathways to mitigate the effects of aging and chronic inflammation.
Humanized Mouse Models in Immunology
The development of advanced humanized mouse models provides significant insights into human immune responses and disease mechanisms. These models can effectively simulate human immune systems by integrating human lymphoid and myeloid cells, enabling the study of T-cell and B-cell functions in a controlled environment. By utilizing humanized mice subjected to vaccinations, researchers can observe authentic neutralizing antibody responses, which can pave the way for new approaches in vaccine development and therapeutic strategies. This innovation represents a major step forward in bridging the gap between murine models and human immunity.
Muscle Inflammation and Brain Communication
Recent findings indicate a strong connection between brain inflammation and muscle dysfunction, highlighting how systemic signals can impair muscle health. In model organisms like Drosophila, infections in the brain activate immune responses that ultimately compromise muscle function without directly targeting muscle tissue. The study suggests a mechanism where inflammatory mediators signal from the brain to skeletal muscle, disrupting mitochondrial activity and leading to fatigue and weakness. This research opens new avenues for exploring treatments that mitigate muscle fatigue arising from central nervous system inflammation.
The Challenges and Rewards of Team Science
The collaborative nature of contemporary scientific research emphasizes the importance of teamwork in overcoming complex challenges. Researchers increasingly rely on diverse expertise to address multifaceted problems, illustrating that successful projects are rarely the result of solitary work. Mentorship and collaboration among peers create a supportive environment for innovation, allowing for the exchange of ideas and resources. Furthermore, the personal rewards of nurturing aspiring scientists and fostering a cooperative spirit enrich the research experience beyond individual contributions.
Dr. Jeffrey Rathmell is the Cornelius Vanderbilt Professor of Immunobiology at the Vanderbilt Center for Immunobiology. His research focuses on T cell metabolism in cancer. He talks about what T cells use for fuel and his work on fatty acid synthesis. He also discusses the ‘obesity paradox’ in cancer immunotherapy and his favorite parts of being a scientist and professor.
Sphinganine Synthesis in Macrophages – Sphinganine biosynthesis is a checkpoint for macrophage pattern recognition in mouse models of sepsis and melanoma.
Brain-Muscle Signaling – Researchers identified a brain-to-muscle signaling axis in Drosophila that regulates muscle performance.
