Ep. 86: “Myeloid Cells” Featuring Dr. Kipp Weiskopf
Aug 27, 2024
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Dr. Kipp Weiskopf, a Valhalla Fellow at the Whitehead Institute, delves into the crucial role of macrophages in cancer therapy. He explains how targeting the CD47/SIRPα axis can promote the destruction of cancer cells. Weiskopf also shares insights on launching spin-off companies aimed at advancing innovative cancer treatments. The conversation explores the complexity of macrophage function within tumors and the emerging therapeutic strategies designed to harness their power for better patient outcomes.
Dr. Kipp Weiskopf emphasizes the significance of targeting the CD47/SIRPα axis to enhance macrophage activity against cancer cells.
The podcast highlights the complexities of regulatory T cells and their instability, which can worsen autoimmune responses and cancer outcomes.
Recent research on gamma delta T cells reveals their unique structural flexibility, enhancing their ability to interact with diverse ligands in immune responses.
Deep dives
Increasing Myeloid Cells for Cancer Targeting
Research focuses on enhancing the ability of myeloid cells to target and eliminate cancer cells. Dr. Kip Weiskopf discusses findings from his studies at the Whitehead and Dana-Farber Institutes, aiming to understand how these cells can be modified for better cancer therapy. By targeting specific interactions within the immune system, the research explores the enhancement of myeloid cell functionalities, which could potentially lead to more effective cancer treatments. Such modifications can help in overcoming the mechanisms that cancer uses to evade immune detection.
Innovations in Immunotherapy and the Role of Immune Checkpoints
The discussion highlights the critical role of immune checkpoints, such as the CD47-SERPα interaction, in regulating macrophage activity against tumors. This checkpoint often inhibits macrophages from attacking cancer cells, leading to poor patient outcomes. Blocking this interaction could activate macrophages, allowing them to recognize and destroy tumor cells more effectively. Furthermore, the conversation explores the potential of bispecific antibodies to enhance macrophage-mediated tumor clearance.
Understanding Regulatory T Cells and Their Function
The podcast delves into the complexities of regulatory T cells (Tregs) and their crucial role in maintaining immune homeostasis. It emphasizes the need for additional markers beyond FOXP3 to accurately identify functionally stable Tregs, as their identity is influenced by several other transcription factors. Research indicates that instability in Tregs can lead to increased levels of interferon-gamma, which diminishes their suppressive functions and promotes autoimmunity. The ongoing exploration of Tregs offers new insights into therapeutic strategies for modulating immune responses in cancer and autoimmune diseases.
Insights into Gamma Delta T Cells
Recent findings on gamma delta T cells reveal their unique structure and flexibility compared to alpha beta T cells. This structural flexibility allows gamma delta T cells to interact with a broader range of ligands, contributing to their versatile roles in immune response. The research elucidates how this promiscuity can impact their function and efficacy in recognizing and attacking tumors. Understanding the specific mechanisms behind gamma delta T cell activation and response provides valuable information for developing targeted immunotherapies.
Impact of Innate Lymphoid Cells in Autoimmunity
The discussion covers the role of innate lymphoid cells (ILCs), particularly in the context of autoimmune diseases such as lupus nephritis. Research indicates that activated ILC1s contribute to organ damage by producing specific inflammatory mediators that exacerbate kidney injury. The study demonstrates that blocking certain receptors on ILCs can alleviate symptoms without affecting overall antibody levels in lupus. This finding suggests potential therapeutic pathways for managing autoimmune conditions by targeting ILC function.
Dr. Kipp Weiskopf is a Valhalla Fellow at the Whitehead Institute. His research focuses on unlocking the therapeutic potential of macrophages for the benefit of cancer patients. He talks about the role of macrophages in the tumor environment and how targeting the CD47/SIRPα axis can induce phagocytosis of cancer cells. He also discusses starting spin-off companies to advance cancer therapies.
Organoids with an Immune Compartment – Researchers generated human intestinal immuno-organoids to investigate intestinal inflammation triggered by cancer-targeting biologics in patients.
Gene Repression in Tregs – The transcription factor Ikaros binds to Foxp3 to inhibit the expression of target genes in Tregs.
γδ T-Cell Antigen Receptor Structure – Scientists used cryo-electron microscopy to determine the structure of of the T-cell receptor found on the surface of γδ T cells.
Autoimmune Organ Damage – Tissue-resident NKp46+ innate lymphoid cells are crucial signal amplifiers of disease-associated macrophage expansion and epithelial cell injury in lupus nephritis.
Monocyte Kit generates millions of monocytes ready for downstream assays or further development into macrophages or dendritic cells.
