Research from The University of Texas MD Anderson Cancer Center has established a link between cancer-associated nerve injury and resistance to immunotherapy. Published in the journal Nature, the study reveals how cancer cells can compromise the protective myelin sheaths around nerves, leading to chronic inflammation. This inflammation contributes to immune exhaustion, ultimately diminishing the effectiveness of immunotherapy treatments.
The team, led by Moran Amit, M.D., Ph.D., a professor of Head and Neck Surgery, emphasizes the need to explore the interactions between cancer and the nervous system, a field referred to as cancer neuroscience. “These findings uncover novel mechanisms by which the immune system and nerves within the tumor microenvironment interact,” Amit stated. He added that these insights reveal actionable targets that could significantly change the approach to immunotherapy resistance in cancer patients.
Understanding Perineural Invasion and Its Implications
Cancer can invade the areas surrounding nerves, a phenomenon known as perineural invasion. This condition is associated with poorer prognoses and increased treatment complexity across various cancer types. Despite its prevalence, the relationship between this invasion and the immune system is not well understood.
The study focused on the implications of perineural invasion and nerve injury in patients with squamous cell carcinoma, melanoma, and stomach cancer. Collaborating with the immunotherapy platform at the James P. Allison Institute, the research team employed advanced genetic, bioinformatics, and spatial techniques to analyze trial samples.
Key findings revealed that cancer cells actively degrade myelin sheaths, which leads to nerve injury. This injury prompts an inflammatory healing response, but as tumors grow, they repeatedly damage the nerves. The resulting chronic inflammation exhausts the immune system, fostering an immunosuppressive tumor microenvironment that contributes to treatment resistance.
Impacts on Treatment Strategies and Future Research
The study demonstrated that by targeting the pathways associated with cancer-induced nerve injury, it is possible to reverse this resistance and enhance treatment responses. Notably, the authors stressed that the decline in neuronal health is closely linked to perineural invasion and nerve injury, rather than being a generalized effect of cancer. This underscores the significance of understanding cancer-nerve interactions in relation to cancer progression.
As part of MD Anderson’s Cancer Neuroscience Program, researchers are delving into various themes, including neurobiology, brain and spine tumors, neurotoxicities, and neurobehavioral health. The goal is to elucidate how the nervous system interacts with cancer and how these interactions affect patients throughout their treatment journeys.
This multi-institutional study involved a global collaboration among MD Anderson, Brigham and Women’s Hospital, the University of Michigan, Moffitt Cancer Center, and Queens University. It received partial support from the James P. Allison Institute and the Cancer Neuroscience Program at MD Anderson. A complete list of collaborating authors and their disclosures is available in the published paper.
