MSK Research Highlights, September 25, 2025

(Press-News.org) New research from Memorial Sloan Kettering Cancer Center (MSK) highlights the importance of tumor location in metastasis; shows how regulatory T cells work with sensory nerves in the skin to restrain pain and inflammation; explores whether a large language model can adequately summarize cancer patients’ experiences with pain; and finds proton therapy is effective at treating leptomeningeal metastasis.

In metastasis, genetics meet geography, study finds Mutations that drive the growth and survival of cancer cells can help a primary tumor spread to new sites, but the extent to which they help sustain tumor growth at these metastatic sites has been unclear.

An MSK-led research team — led by first author Kaloyan Tsanov, PhD, a former postdoc at MSK who now heads his own lab at the University of Chicago — looked for answers using one such gene, SMAD4, which is commonly inactivated by mutations in gastrointestinal cancers.

The scientists used a mouse model of pancreatic cancer to study whether metastatic tumors remain dependent on SMAD4 deactivation by turning off the gene in early tumor development and later reactivating it in established metastases. Interestingly, they found reactivating SMAD4 had different effects based on the location of the metastasis. It suppressed liver metastases but encouraged the expansion of lung metastases.

“We found that different organ sites select for different cell types present in the primary tumor, and that this can dramatically alter what they need to remain viable,” says senior study author Scott Lowe, PhD, Chair of the Cancer Biology and Genetics Program at MSK’s Sloan Kettering Institute.

“The broader implication is that the effectiveness of some therapies may not only be related to the gene mutations in the tumors, but also where in the body these tumor cells reside,” Dr. Tsanov adds. in Nature Cancer. 

How regulatory T cells work with sensory nerves in the skin to restrain pain and inflammation Nerve endings in our skin help protect us by sensing a variety of stimuli, including extreme temperature, physical forces, tissue damage, and infection — and by generating sensations like itching or pain. But a growing body of work suggests that these neuronal cells also help mobilize an immune response when confronted with threats.

New MSK research — led by Alejandra Mendoza, PhD, a postdoc in the lab of senior study author Alexander Rudensky, PhD, at the Sloan Kettering Institute — examined the relationship between regulatory T cells (Tregs) and these peripheral neurons. (Dr. Mendoza is now an assistant professor of immunology and microbiology at Scripps Research.)

Tregs are key immune cells that promote tolerance to “self” and to helpful bacteria, harmless food allergens, and long-term infections. Using mouse models of psoriasis-like inflammation, the research team determined that Tregs play an important role in limiting overactivation of sensory neurons in the skin — thereby limiting inflammation — at the early stages of an infection. The researchers also found that Treg expression of Penk — a gene that encodes a neuropeptide called enkephalin, which produces an analgesic effect — is essential to Treg cells’ ability to help regulate the body’s response to pain.

Overall, the study suggests that Tregs, by acting as a part of a mixed immune cell-neuronal circuit, play a vital role in keeping the body from excessive responses when the skin encounters a new threat. in Science Immunology. (The study was also highlighted in the ScienceAdviser newsletter.)

Studying whether a large language model can adequately summarize cancer patients’ experiences with pain Patient-reported outcomes (PROs) have become a critical component of clinical research to assess the benefits of new medical therapies, including treatments for cancer. These outcomes include factors that affect a patient’s quality of life, such as fatigue, mood, and pain. PROs are generally collected by asking patients to fill out questionnaires, but researchers, including those at MSK, are studying whether large language models like ChatGPT could help to capture PROs in a patient’s own words.

As part of that effort, an MSK team co-led by outcomes research scientist Talya Salz, PhD, and behavioral scientist Thomas Atkinson, PhD, recently received a grant from the nonprofit Patient-Centered Outcomes Research Institute (PCORI) to study how an algorithm guided by a large language model could help identify themes related to the experience of cancer pain from narrative reports. Using the model, named PainReporter, the team will evaluate the extent to which the themes identified by the model agree with conventional PROs metrics of pain. They will also evaluate how patients perceive the accuracy the PainReporter summary and their experiences using the model. Learn more about this project on the PCORI website.

Proton therapy effective at treating leptomeningeal metastasis Leptomeningeal metastasis (LM) is a serious condition in which cancer spreads to the fluid and tissues surrounding the brain and spinal cord. New results from a randomized phase 2 clinical trial at MSK show that craniospinal proton therapy, an advanced form of radiation therapy, is effective in controlling LM.

In LM patients who received proton therapy to the brain and spinal cord (also called proton craniospinal irradiation), the disease remained stable more than three times longer than in those who got conventional radiation to just the brain or portions of the spinal cord. Patients receiving proton craniospinal therapy also lived more than twice as long.

Earlier results were presented in 2022 at the annual meeting of the American Society of Clinical Oncology (ASCO) by Jonathan Yang, MD, PhD, who has since left MSK. Dr. Yang collaborated closely with neuro-oncologist Adrienne Boire, MD, PhD, who has devoted her research to finding additional ways to block LM.

“This work shows that it is essential to treat both the brain and the spinal cord when treating LM. It’s very exciting that we have an effective new option for a disease that is very hard to treat,” Dr. Boire says. “Previous radiation techniques did not allow us to treat the brain and spinal cord. These results show that proton therapy should be considered when it is available.” in JAMA Oncology.

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