Ep. 41: “Autoimmunity and Cancer Immunotherapy” Featuring Dr. Vijay Kuchroo
Nov 8, 2022
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Dr. Vijay Kuchroo, the Samuel L. Wasserstrom Professor of Neurology at Harvard Medical School, delves into the fascinating interplay of autoimmunity and cancer immunotherapy. He highlights the essential conditions for differentiating Th17 cells and their critical roles in autoimmune diseases. A significant revelation includes his lab’s discovery of Tim-3, a novel T cell inhibitor receptor now being leveraged for cancer treatments. The conversation is enriched with insights on the impacts of anti-CTLA-4 antibodies on the tumor microenvironment, making it a must-listen for immunology enthusiasts.
Dr. Vijay Kuchroo explains how Th17 cells play a critical role in bridging autoimmune responses and cancer immunotherapy through specific cytokine influences.
Research highlights the implications of impaired calcium signaling in severe immunodeficiencies, significantly affecting T and B cell activation mechanisms.
Novel findings on CTLA-4 antibodies reveal their ability to reprogram the tumor microenvironment, enhancing anti-tumor immune responses beyond just blocking signals.
Deep dives
The Intersection of Autoimmunity and Cancer Immunotherapy
Cancer immunotherapy, particularly the role of immune checkpoint inhibitors, is significantly impacted by the mechanisms underlying autoimmune diseases. Recent research by Dr. Vijay Khatru highlights how certain T cell populations, like Th17 cells, contribute to this intersection, with specific cytokines influencing their behavior. Through effective differentiation conditions, Th17 cells can mediate inflammatory responses that promote either cancer progression or autoimmunity. Understanding these relationships can help design better therapeutic strategies targeting these immune pathways.
Calcium Signaling Deficiencies and Immunodeficiency
New findings have emerged regarding patients with severe immunodeficiencies tied to mutations in inositol 1,4,5-trisphosphate (IP3) receptor genes. Research detailing the genetic backgrounds of two such patients reveals how impaired calcium signaling leads to dysfunction in T and B cell activation. Specific mutations were identified that result in varying degrees of immunological impact, shedding light on how calcium transport from the endoplasmic reticulum is crucial for immune responses. This work may expand the understanding of calcium-related disorders in immunology.
Light Chain Coherence in Antibody Response
A novel study revealed that the immunological memory involves a significant coherence between heavy and light chain antibodies, particularly in memory B cells. The research shows that when comparing different individual responses, if a heavy chain is the same, the light chains match in approximately 80% of cases. This phenomenon was mostly observed in memory B cells rather than naive cells, indicating a possible advantage for memory responses in effective immunization. The implications of these findings could influence how antibodies are evaluated and utilized in diverse therapeutic contexts.
Mechanisms Behind CTLA-4 Checkpoint Inhibition
Recent insights into CTLA-4 antibodies have unveiled a complex mechanism that extends beyond simply blocking inhibitory signaling on T cells. Instead, these antibodies activate myeloid cells through engagement with FC gamma receptors, leading to significant reprogramming of the tumor microenvironment. Evidence suggests that the depletion of regulatory T cells, alongside enhanced infiltration of pro-inflammatory myeloid cells, contributes to tumor rejection. Understanding how CTLA-4 interacts with immune elements in the tumor microenvironment provides a deeper understanding of therapies aimed at reversing immune suppression in cancer.
Enhancing Immunity through Intranasal Vaccination
Research into intranasal vaccines demonstrates their promise in eliciting mucosal immunity against respiratory viruses, highlighting the efficacy of these approaches in boosting IgA responses. Studies indicate that following an initial mRNA vaccination, subsequent intranasal boosters may reduce viral transmission, presenting an innovative way to bolster immunity. Particularly, the use of intranasal vaccines shows potential in mitigating the spread of viruses not just in vaccinated individuals but to those around them as well. The exploration of these non-invasive vaccination methods could reshape vaccine strategies in the fight against viral outbreaks.
Dr. Vijay Kuchroo is the Samuel L. Wasserstrom Professor of Neurology at Harvard Medical School. His major research interests include the role of co-stimulation in autoimmune diseases, as well as cell surface molecules and regulatory factors that regulate the induction of T cell tolerance and dysfunction. He talks about the conditions necessary to differentiate Th17 cells and their role in autoimmunity. He also discusses his group’s discovery of Tim-3, an inhibitor receptor on T cells which is now being exploited for cancer immunotherapy.
Disrupting Calcium Homeostasis – Researchers showed that inherited variants in ITPR3 alter physiologically relevant Ca2+ signaling responses, driving defects in immune responses.
Light Chain Coherence in Antibodies – Among naturally occurring antibodies that have adapted to particular antigens, those with similar heavy chains usually have similar light chains.
