Researchers from the Technical University of Munich (TUM) and Ludwig-Maximilians-Universität München (LMU) Hospital have identified a new mechanism that tumors use to evade the immune system. This breakthrough could lead to improved cancer immunotherapies, potentially helping treatments work better for more patients. The findings are detailed in two studies published in the journal Nature.
The role of prostaglandin E2
Tumors secrete a substance called prostaglandin E2 (PGE2), which plays a crucial role in hindering the body's immune response. PGE2 affects stem-like T cells, which are crucial for developing cytotoxic T cells that attack cancer cells. When PGE2 binds to receptors on these T cells, it prevents them from multiplying and transforming into cancer-fighting cells, effectively allowing the tumor to grow unchecked.
Mechanism uncovered
The research team, led by Dr. Jan Böttcher from TUM and Prof. Sebastian Kobold from LMU, discovered that blocking the interaction between PGE2 and its receptors (EP2 and EP4) enables the immune system to combat tumors more effectively. This suggests that targeting PGE2 could significantly enhance the effectiveness of existing cancer therapies.
Implications for current treatments
Current immunotherapies often target a later phase of the immune response. For instance, checkpoint inhibitors work by reactivating exhausted cytotoxic T cells. However, if tumors can be prevented from switching off the immune response at an early stage by blocking PGE2, these treatments could become even more effective.
Supporting evidence
A second study confirmed these findings by showing that blocking PGE2 in human tumor samples led to better T cell expansion and improved cancer-fighting capability. This collaborative effort involved researchers from the University Hospital of Lausanne.
Looking ahead
Dr. Böttcher emphasizes the importance of developing new strategies to counteract the effects of PGE2. This could involve preventing tumors from producing PGE2 or making immune cells resistant to it. Such advancements could open new pathways for significantly improving the outcomes of cancer immunotherapies.
Publications
For those interested in the scientific details, the findings are documented in the following studies:
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Prostaglandin E2 curtails interleukin-2-dependent effector expansion from tumour infiltrating stem-like CD8+ T cells to promote cancer immune escape. Nature (2024). DOI: 10.1038/s41586-024-07254-x
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PGE2 inhibits TIL expansion by disrupting IL-2 signalling and metabolism. Nature (2024). DOI: 10.1038/s41586-024-07352-w
These studies provide a deeper understanding of how tumors evade the immune system and propose new ways to enhance cancer immunotherapy, bringing hope for more effective treatments in the future.
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