Moffitt study uncovers new mechanism of immunotherapy resistance
Cancer-induced nerve injury weakens anti-PD-1 treatment, but novel approaches may overcome it
2025-08-21
(Press-News.org) TAMPA, Fla. (Aug. 21, 2025) — A new international study led by researchers at Moffitt Cancer Center, the Karolinska Institutet and the University of Texas MD Anderson Cancer Center has uncovered a surprising mechanism of resistance to immunotherapy: cancer’s ability to injure nearby nerves.
The study, published in Nature, shows that when cancer cells infiltrate and damage tumor-associated nerves, it triggers an inflammatory response that ultimately weakens the effectiveness of anti-PD-1 immunotherapy. This widely used treatment works by unleashing the body’s immune system to attack tumors, but many patients fail to respond.
“Our findings demonstrate that cancer-induced nerve injury is not just a bystander effect, it directly shapes the immune environment in ways that allow tumors to evade treatment,” said Kenneth Tsai, M.D., Ph.D., co-corresponding author of the study and co-director of Moffitt’s Donald A. Adam Melanoma and Skin Cancer Center of Excellence. “Importantly, we also found that this process is reversible.”
Using patient samples including those from recent neoadjuvant therapy trials and preclinical models of cutaneous squamous cell carcinoma, melanoma, gastric cancer and pancreatic cancer, the team showed that cancer cells degrade the protective myelin sheath of nearby nerves. The injured neurons release inflammatory signals, including IL-6 and type 1 interferons, which is able to be repaired initially, but over time creates a chronically suppressive tumor microenvironment.
The researchers tested several strategies to disrupt this cycle. Resistance to anti-PD-1 therapy was overcome by removing nerves that transmit pain, blocking key neuronal injury signals, or combining anti-PD-1 with drugs that target the IL-6 pathway.
“This work highlights a new role for the nervous system in cancer progression and resistance to therapy,” Tsai said. “By targeting the signaling that follows nerve injury, we may be able to restore the immune system’s ability to fight cancer.”
The discovery could lead to new treatment combinations that improve outcomes for patients whose tumors invade and grow along nerves, a common feature in several cancer types associated with poor prognosis.
“This is an example of how studying the cross talk between cancer, nerves and the immune system can reveal entirely new actionable vulnerabilities,” Tsai said.
The study was supported by the National Institutes of Health (CA016672, P30CA016672 and P30-CA076292).
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 57 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, X, Instagram and YouTube.
###
END
ELSE PRESS RELEASES FROM THIS DATE:
2025-08-21
New experiments by Christian Wood and colleagues suggest that the marmoset brain area 46 (A46) in the dorsolateral prefrontal cortex is key to a functional network that regulates positive and negative emotion-related processes. The findings relate directly to motivation and responsiveness to threat, which play important roles in depression and anxiety. The study also sheds some light on how non-invasive treatments such as transcranial magnetic stimulation and the drug ketamine may work within the dorsolateral prefrontal cortex to reduce depression and anxiety. Wood et al. show that inactivation of A46 blunts reward-seeking behavior (a hallmark of depression) ...
2025-08-21
A collaborative team of researchers from the University of California, Berkeley, the Georgia Institute of Technology, and Ajou University in South Korea has revealed that the unique fan-like propellers of Rhagovelia water striders —which allow them to glide across fast-moving streams—open and close passively, like a paintbrush, ten times faster than the blink of an eye. Inspired by this biological innovation, the team developed a revolutionary insect-scale robot that incorporates engineered self-morphing fans that mimic ...
2025-08-21
In the past decade there has been significant interest in studying the expression of our genetic code down to the level of single cells, to identify the functions and activities of any cell through the course of health or disease.
The identity of a cell, and the way that identity can go awry, is critical to its role in many of the biggest health challenges we face, including cancer, neurodegeneration, or genetic and developmental disorders. Zooming in on single cells allows us to tell the difference between variants which would otherwise be lost in the average of a region. This is essential for finding new medical solutions to diseases.
Most single cell ...
2025-08-21
Thousands of years ago, ancient humans undertook a treacherous journey, crossing hundreds of miles of ice over the Bering Strait to the unknown world of the Americas.
Now, a new study led by the University of Colorado Boulder suggests that these nomads carried something surprising with them—a chunk of DNA inherited from a now-extinct species of hominin, which may have helped humans adapt to the challenges of their new home.
The researchers will publish their results Aug. 21 in the journal Science.
“In terms of evolution, this is an incredible ...
2025-08-21
Irvine, Calif. — Researchers at the University of California, Irvine and other institutions have spotted a contradiction in worldwide wildfire trends: Despite a 26 percent decline in total burned area from 2002 to 2021, the number of people exposed to wildfires has surged by nearly 40 percent.
The study, published today in Science, revealed another statistic that may come as a surprise to people who rely primarily on Western news sources: While high-profile wildfire disasters in the United States, Canada and Australia often dominate headlines, the researchers found that 85 percent of all human exposures to wildfires during that period occurred in ...
2025-08-21
PROVIDENCE, R.I. [Brown University] — A new study provides fresh evidence that ancient interbreeding with archaic human species may have provided modern humans with genetic variation that helped them adapt to new environments as they dispersed across the globe.
The study, published in Science, focused on a gene known as MUC19, which is involved in the production of proteins that form saliva and mucosal barriers in the respiratory and digestive tracts. The researchers show that a variant of that gene derived from Denisovans, an enigmatic species of archaic humans, is present in modern Latin ...
2025-08-21
New research, published today in the journal Science, shows how lysosomes — organelles that act like cells’ waste disposal system — respond to stress by becoming abnormally bloated, a process called lysosomal vacuolation that is associated with numerous diseases.
Essential for cellular health, well-functioning lysosomes are also linked with healthy aging, so better understanding of the steps involved in vacuolation could eventually inform new therapies to treat diseases or promote healthy aging, according to senior author Jay Xiaojun Tan, Ph.D., assistant ...
2025-08-21
A new Stanford study challenges the decades-old view that the rise of land plants half a billion years ago dramatically changed the shapes of rivers.
Rivers generally come in two styles: braided, where multiple channels flow around sandy bars, and meandering, where a single channel cuts S-curves across a landscape. Geologists have long thought that before vegetation, rivers predominantly ran in braided patterns, only forming meandering shapes after plant life took root and stabilized riverbanks.
The new study, which will be published online by the journal Science on Thursday, Aug. 21, 2025, suggests the theory that braided rivers ...
2025-08-21
UNIVERSITY PARK, Pa. — When a disease-causing virus or other organism is transmitted from one species to another, most of the time the infection sputters and dies out. On rare occasions, the infection can perpetuate transmission in the new host species and cause a pandemic. For example, scientists are keeping a close eye on H5N1 highly pathogenic avian influenza, which causes bird flu and has been found in cows and humans. But is there a way to anticipate when infections will die out on their own and when they will persist?
New research, led by scientists at Penn State and the University of Minnesota Duluth, identified certain characteristics that could help predict whether ...
2025-08-21
Polaritons are formed by the strong coupling of light and matter. When they mix together, all the matter is excited simultaneously – referred to as delocalization. This delocalization has the unique ability to relay energy between matter that is otherwise not possible.
Disordered energy is ubiquitous in nature and the universe. Disordered energy is less organized and less available to do work, such as with heat dissipation. Even in plants, disorder can ruin effective energy transfer. In the context of polaritons, as disorder increases, it can negatively affect light-matter ...
LAST 30 PRESS RELEASES:
[Press-News.org] Moffitt study uncovers new mechanism of immunotherapy resistance
Cancer-induced nerve injury weakens anti-PD-1 treatment, but novel approaches may overcome it
