Ep. 82: “Immunological Memory” Featuring Dr. Susan Kaech
Jul 2, 2024
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Dr. Susan Kaech, a leading immunologist at the Salk Institute, discusses her groundbreaking research on memory T cells and T cell exhaustion, shedding light on why they sometimes fail to provide lasting immunity. She shares insights into neuroimmunology, revealing how stress impacts T cell behavior and immune function. Kaech also reflects on her unique journey from genetics to immunology, emphasizing the importance of understanding memory in infections and cancer. A fascinating exploration of the immune system's complexity!
Dr. Susan Kaech emphasizes that the differentiation of memory T cells is influenced by the duration of antigen exposure and activation signals.
The safety concerns surrounding CAR T-cell therapy highlight the potential risk of secondary malignancies post-treatment due to existing genetic predispositions.
Exploring the communication between T cells and the nervous system reveals that stress responses may impair T cell function during chronic infections.
Deep dives
Memory T-Cell Development Insights
Dr. Susan Keck's research focuses on memory T-cell development, a crucial aspect of adaptive immunity. The discussion highlights how memory T cells are formed during immune responses, emphasizing that not all activated T cells will progress to memory. Factors influencing memory cell differentiation include the duration of antigen exposure and the nature of signals received during activation. Understanding these mechanisms can inform strategies for improving vaccine efficacy and therapies for chronic infections.
Impacts of CAR T-Cell Therapy
The safety of CAR T-cell therapy has been a growing concern, particularly regarding the risk of secondary malignancies. Analysis of data from over 12,000 treatments revealed that approximately 4.3% of patients developed new cancers post-therapy, prompting investigations into the oncogenic potential of genetically modified T cells. The findings suggest that previously existing genetic predispositions, rather than the CAR T modifications, may contribute to these secondary tumors. The need for ongoing monitoring and understanding of the long-term implications of CAR T-cell therapy has become apparent in the field.
Bacterial Glycan Breakdown Mechanisms
A recently published study explores an alternative pathway for bacterial glycan breakdown, shedding light on the enzymatic functions of glycosidases. Researchers identified new non-causal glycosidase activities that can cleave various substrates, thus broadening our understanding of how bacteria process complex carbohydrates. This discovery is significant not only for microbiology but also for its potential implications for drug metabolism within the human microbiome. The findings highlight the evolutionary adaptability of bacteria and their biochemical versatility.
Neuroimmunology: Nerve Influence on T Cells
Recent findings indicate that the communication between T cells and nerves can affect T cell function and exhaustion. The presence of adrenergic receptors on exhausted T cells signals that stress responses may impair T cell activity in chronic infection scenarios. This connection invites further inquiry into how the nervous system influences immune responses, especially in the context of cancer and viral infections. Understanding this interplay could lead to new therapeutic strategies targeting both the immune and nervous systems.
Bile Acids, Microbiome, and T Cell Function
Research into bile acids has revealed their role in regulating T cell functions, especially in the context of liver cancer. Elevated bile acids in tumor environments can hinder T cell efficacy, underscoring the importance of metabolic adaptations in immune responses. Furthermore, interactions between the microbiome and bile acid metabolism can modulate T cell activity, with some secondary bile acids enhancing or suppressing immune responses. This underscores the intricate balance between diet, microbiome health, and immune system functionality.
Dr. Susan Kaech is a Professor and Director of the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute. Her lab aims to understand how memory T cells are produced during infection and vaccination, how they function, and why they can fail to induce long-term immunity, particularly during chronic disease or cancer. In this episode, she talks about her research on T cell exhaustion and neuroimmunology, as well as her path from genetics to immunology.
Glycan Breakdown and Bacterial Function – Researchers used a large-scale screen to identify enzyme systems that represent an underappreciated mode of glycan degradation.
Cancer Risk after CAR T Therapy – Only a small percentage of patients who receive CAR T therapies develop secondary cancers, and most are not directly linked to CAR T treatment.
CD8+ T Cells in Hepatitis B – Hepatocellular priming induces key co-signaling receptors in dysfunctional CD8+ T cells.
T Cell Aging – T cell epigenetic clocks measure replicative history and can continue to accumulate well-beyond organismal lifespan.
-XF.
