Ep. 32: “Memory T Cell Responses” Featuring Dr. Laura Mackay
Jul 5, 2022
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In this discussion, Dr. Laura Mackay, a Professor at the Peter Doherty Institute, dives into her groundbreaking research on tissue-resident memory T cells. She highlights their role in cancer therapy and collaborates with Pfizer to explore new treatment targets. The conversation uncovers intriguing links between sleep and cancer metastasis, alongside how gut metabolites aid nerve repair. Additionally, Mackay sheds light on T cell exhaustion and the significance of effective communication in academic and industry collaborations.
Memory T cells, particularly tissue-resident memory T cells, play a vital role in providing quicker immune responses to recurrent infections.
Circadian rhythms influence cancer progression by affecting the timing of metastatic cell shedding, with potential implications for treatment strategies.
Harnessing pre-existing T-cell responses against cytomegalovirus can enhance cancer therapy by modifying the tumor microenvironment and activating immune responses.
Deep dives
Memory T-Cell Responses
Research on memory T-cell responses reveals their crucial role in immune protection against recurrent infections. Tissue resident memory T-cells (TRMs) do not circulate but remain in specific tissues where previous infections occurred, allowing for quicker immune responses upon re-exposure. These cells can be identified by specific markers like CD69 and CD103, which help in their retention within tissues. This research highlights the need for advanced techniques to further understand TRM biology and their functional properties in various tissues.
Circadian Rhythms and Cancer
Circadian rhythms significantly impact cancer progression, with recent findings indicating that cancer cells may shed more metastatic cells during sleep. Changes in hormone levels during the night, including melatonin and glucocorticoids, have been shown to influence tumor behavior and immune surveillance. Experimental studies using mouse models provided evidence that the timing of cell shedding correlates with enhanced growth and spread of tumors. This connection underlines the importance of understanding circadian biology in cancer treatment strategies.
Cytomegalovirus and Tumor Immunotherapy
Harnessing pre-existing T-cell responses against cytomegalovirus (CMV) shows promise in cancer therapy by altering the tumor microenvironment. CMV infection leads to durable CD4 and CD8 T-cell responses, which can infiltrate tumors. By using specific immunogenic epitopes from CMV, researchers demonstrated enhanced immune activation in tumor models and the potential for complete tumor regression. This approach suggests that leveraging the immune memory against common viruses could improve cancer immunotherapy outcomes.
Gut Metabolites and Nerve Repair
The gut metabolite indole-3-propanoate (IPA) has been linked to enhanced nerve regeneration, influenced by intermittent fasting. Research indicates that gut bacteria, particularly Clostridium sporogenes, are key producers of IPA, which promotes neutrophil chemotaxis and aids in nerve repair following injury. When mice underwent fasting, increased levels of IPA contributed to improved outcomes in nerve regeneration without hypersensitivity. This discovery hints at potential therapeutic applications of gut microbiome modulation for injury recovery.
Regulatory T-Cells and Hair Growth
Regulatory T-cells (Tregs) play a vital role in hair follicle regeneration by regulating the local stem cell niche via glucocorticoid signaling. Research has shown that glucocorticoid receptors in Tregs facilitate hair regrowth following damage, indicating their significance in repair mechanisms. The study identified TGF-beta-3 as a key factor that mediates the interaction between Tregs and hair follicle stem cells, promoting hair proliferation. These findings could lead to new insights and strategies for treating hair loss conditions.
Dr. Laura Mackay is a Professor and Laboratory Head at the Peter Doherty Institute for Infection and Immunity at the University of Melbourne. She talks about her tissue-resident memory T cell research and her ongoing collaboration with Pfizer to identify and validate new targets for cancer therapy.
