Researchers at TUM and LMU have discovered how tumors prevent the formation of immune responses by cytotoxic T cells, which are crucial in fighting cancer. The study published in Nature identifies how tumors use the messenger substance prostaglandin E2 to influence immune cells, inhibiting the development of cytotoxic T cells within the tumor. By binding to specific receptors on immune cells, prostaglandin E2 hinders the differentiation process, leading to a collapse of the immune response and allowing the tumor to progress.
Current cancer immunotherapies target the later stages of the immune response, such as checkpoint inhibitor therapies that aim to reinvigorate exhausted T cells. However, the research by Dr. Jan Böttcher and Prof. Sebastian Kobold highlights the importance of addressing the early phase of the immune response, where tumors prevent stem-like T cells from generating cytotoxic T cells within the tumor. By blocking the interaction between prostaglandin E2 and its receptors in tumor models, the immune system was able to effectively fight against tumors.
The findings suggest that existing therapies could be more effective if the effects of prostaglandin E2 on stem-like T cells are blocked, allowing for their unimpeded differentiation within tumor tissue. This approach could increase the success of immunotherapies that rely on stimulating T cells, such as those involving the protein IL-2. By disrupting the binding of prostaglandin E2 to its receptors, T cells may be able to respond to IL-2 and successfully combat cancer.
A second study published in Nature further confirms the impact of prostaglandin E2 on the immune system. Researchers from the University Hospital of Lausanne collaborated with the Munich team to investigate the effects of blocking prostaglandin E2 release in human tumor tissue. They found that inhibiting the messenger substance led to better expansion of T cells, allowing them to effectively target human cancer cells. These results provide a concrete starting point for enhancing immunotherapies by overcoming tumors’ defense mechanisms.
Moving forward, researchers worldwide are tasked with developing strategies to counteract the effects of prostaglandin E2 in tumors. This could involve preventing tumors from producing the molecule or making immune cells resistant to its influence. By focusing on disrupting the early phase of the immune response and enabling the unhindered differentiation of T cells within tumor tissue, new approaches to cancer immunotherapy may be developed to improve treatment outcomes and increase the effectiveness of existing therapies. The study’s findings offer valuable insights into the potential mechanisms that could be targeted to enhance the body’s immune response against cancer.
