A new international study led by researchers at Moffitt Cancer Center, Karolinska Institutet and the Cancer Center of the University of Texas MD Anderson has revealed an amazing immunotherapy resistance mechanism: Cancer’s ability to injure nearby nerves.
The study, published in NatureIt shows that when cancer cells penetrate and damage the tumor-related nerves, it causes an inflammatory response that ultimately weakens the effectiveness of anti-1 immunotherapy. This widely used treatment works by releasing the body’s immune system to attack tumors, but many patients do not respond.
Our findings show that nerve -cancer induced injury is not just a phenomenon of those present, directly shapes the immune environment in ways that allow tumors to avoid treatment. It is important that we also found that this process is reversible. ”
Kenneth TSAI, MD, Ph.D., co-opposing the author of the study and co-director of Donald A. Adam Melanoma of Moffitt and Cancer Cancer
Using patient samples, including those of recent treatment tests with neo -operative and preclinical models of skin cell, melanoma, gastric and pancreatic cancer, the group showed that cancer cells degrade the myelin protective case. Injured neurons release inflammatory signals, including IL-6 and type 1 interferon, which can be repaired initially, but over time create a time-tumor-end-end-end-end.
The researchers examined several strategies to disrupt this cycle. Resistance to anti-1-1 treatment was exceeded by removing the nerves that transmit pain, preventing basic signals of neuronal damage or combining anti-1-1 with drugs aimed at IL-6.
“This project highlights a new role for the nervous system in cancer development and resistance to treatment,” TSAI said. “By targeting the signaling that follows nerve injury, we may be able to restore the immune system’s ability to combat cancer.”
The discovery could lead to new combinations of treatment that improve the results for patients whose tumors invade and develop along the nerve, a common feature in various types of poor prognosis.
“This is an example of how the study of cross -speech between cancer, nerve and immune system can reveal completely new offers that can be activated,” TSAI said.
The study was supported by the National Institutes of Health (CA016672, P30CA016672 and P30-CA076292).
Source:
Magazine report:
Baruch, en, et al. (2025) Cancer-induced nerve damage promotes resistance to anti-1-1 treatment. Nature. Doi.org/10.1038/S41586-025-09370-8.
