Williams Cancer Institute

Cracking the Code: Unraveling Tumors’ Immune Evasion Tactics

In the ongoing battle against cancer, understanding how tumors evade immune responses is crucial. Researchers from the Technical University of Munich (TUM) and the Ludwig-Maximilians-Universität München (LMU) Hospital have made a significant breakthrough in this area, revealing the intricate mechanisms through which tumors actively thwart the body’s immune defenses.

Published in the prestigious journal Nature, their groundbreaking study sheds light on a previously unknown aspect of tumor immunology. By deciphering these mechanisms, the researchers have paved the way for the development of innovative cancer immunotherapies that could potentially revolutionize cancer treatment.

In their quest to understand how tumors suppress immune responses, the research team led by Dr. Jan Böttcher and Prof. Sebastian Kobold uncovered a pivotal role played by a messenger substance known as prostaglandin E2. This substance, secreted by many cancer cells, acts on specific receptors present on immune cells, inhibiting their ability to mount an effective immune response against the tumor.

Prostaglandin E2 binds to receptors known as EP2 and EP4 on certain immune cells, preventing them from maturing into cytotoxic T cells—the body’s frontline warriors against cancer. This disruption of the immune response allows tumors to evade detection and proliferation continues unchecked.

The findings have profound implications for cancer immunotherapy, which aims to harness the body’s immune system to target and destroy cancer cells. Current immunotherapy approaches focus on reversing the suppression of fully differentiated cytotoxic T cells. However, the researchers suggest that blocking the effects of prostaglandin E2 on stem-like T cells could enhance the effectiveness of these treatments.

Moving forward, the researchers advocate for the development of strategies to overcome tumors’ defense mechanisms. By targeting prostaglandin E2 or rendering immune cells resistant to its effects, they believe it may be possible to unleash the full potential of the body’s immune system in the fight against cancer.

This groundbreaking research represents a collaborative effort between institutions, with researchers from the University Hospital of Lausanne also contributing to the findings. Together, they have provided a concrete starting point for enhancing cancer immunotherapies and bringing new hope to patients battling this devastating disease.

In conclusion, the discovery of how tumors suppress immune responses marks a significant milestone in cancer research. By unraveling these complex mechanisms, researchers are poised to develop more effective treatments that could ultimately save lives and transform the landscape of cancer care.

Reference: Morotti, M., Grimm, A.J., Hope, H.C. et al. PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function. Nature (April 24, 2024). https://doi.org/10.1038/s41586-024-07352-w
Lacher, S.B., Dörr, J., de Almeida, G.P. et al. PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells. Nature (April 24, 2024). https://doi.org/10.1038/s41586-024-07254-x

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