Cancer cells break down the nerve covers that cause immune exhaustion and resistance to therapy

Cancer cells can break down the protective covers around the nerves, causing nerve injuries that trigger chronic inflammation that leads to immune exhaustion and eventual immunotherapy resistance, according to a new research from the MD Cancer Center of the University of Texas.

The study, published today in Nature, underlines the importance of investigating the interactions between cancer and the nervous system, a field known as cancer neuroscience. The results suggest that addressing the signaling routes involved can reverse this inflammation and improve treatment responses.

These findings discover new mechanisms by which the immune system and nerves within the tumor microenvironment interact, revealing processable objectives that could transform the way we address immunotherapy resistance in cancer patients. This marks a significant advance in our understanding of immune dynamics to tumor-neuro-inmune, highlighting the importance of investigating cancer interaction and neuroscience in significant ways that can directly affect clinical practice. “

Moran Amit, MD, Ph.D., correspondence author, professor of head and neck surgery

Tumors can sometimes infiltrate space around the nerves and fibers of the nervous system that are very close, a process known as perineural invasion, which leads to a bad prognosis and a escalation of treatment in various types of cancer. However, little is known about how this invasion affects or interacts with the immune system.

The study, co-dried by AMIT, Neil Gross, MD, professor of head and neck surgery, and Jing Wang, Ph.D., professor of Bioinformatics and Computational Biology, examined the role of perineural invasion and cancer cancer and stomach cancer in relation to the development of the resistance to common immunotherapy in patients with patient cell stomach cancer.

Collaborating with the immunotherapy platform, part of the James P. Allison Institute, the team analyzed test samples using genetic, bioinformatic and spatial techniques advanced. The researchers revealed that cancer cells break down the myelin protective pods that cover nerve fibers, and that injured nerves promote their own healing and regeneration through an inflammatory response.

Unfortunately, this inflammatory response is trapped in a chronic feedback circuit as tumors continue to grow, repeatedly damaging the nerves that then recruit and exhaust the immune system, marking the beginning of an immunosuppressive tumor microambiente that leads to resistance to treatment. The study showed that addressing the nerve injury induced by cancer at different points can reverse this resistance and improve the response to treatment.

It is important to note that the authors point out that this reduction in neuronal health is directly associated with perineural invasion and nerve lesion induced by cancer, instead of a general effect induced by cancer, which highlights the importance of studying cancer interactions that can potentially contribute to cancer progression.

As part of the MD Anderson cancer neuroscience program, researchers are investigating scientific issues, such as neurobiology, brain tumors and spine, neurotoxicities and health of the neuroconductual, to understand how they interact the nervous system and cancer and how this affects patients throughout their cancer trip.

The multi -constitutional study was a global collaboration between MD Anderson, Brigham and Women’s Hospital, the University of Michigan, the Moffitt Cancer Center and the University of Queens. The study was supported by the James P. Allison Institute and the cancer neuroscience program in MD Anderson. You can find a complete list of collaborating authors and their disseminations with the document.