Researchers Discover Why Aggressive Kidney Cancer Subtype Responds to Immunotherapy, Develop Treatment Tool
A study lead by Roswell Park Extensive Cancer Center helps explain why a rare and hyper-aggressive subtype of kidney cancer is susceptible to immunotherapy-information that helped researchers create a first-of-its-kind tool to guide treatment decisions for advanced kidney cancers.
the collaborative work by a team of immunologists and urologists was published in the journal Cancer Cell.
Jason Muhitch, Ph.D., Associate Professor and Co-chair of the Genitourinary Translational Research Group in the Department of Immunology at Roswell Park, and Eric Kauffman, MD, Associate Professor of Oncology in the Departments of Urology and Cancer Genetics & Genomics, are senior authors of the study.
Nicholas Salgia, an MD/Ph.D. candidate through the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo who completed his thesis work in the lab of Dr. Muhitch is the first author.
the new insights arose from observations about sarcomatoid renal cell carcinoma (sRCC), an aggressive subtype comprising 5% of all cases of kidney cancer. While this subtype, typically diagnosed in the late stages, is resistant to most anti-cancer therapies, a type of immunotherapy called immune checkpoint inhibitors ofen proves effective.
New Genomic Signature Could Predict Immunotherapy Response in Kidney Cancer
For patients with advanced kidney cancer considering either immunotherapy or targeted therapy, until now there has been no reliable tool for determining wich patients would benefit most from one treatment or the other. The research team created a tool called a genomic dedifferentiation signature (GDS) to meet that need.
“This tool holds promise as a biomarker for guiding decisions in advanced kidney cancer,” says Dr. Muhitch.
“We identified a set of genes that were increased in these aggressive tumors, and from this set of genes, we created a novel gene signature that can identify patients with aggressive disease who are also primed to respond to immune-based cancer therapy.”
Adds Dr. Kauffman, who is also a staff physician at Roswell Park, specializing in the care of kidney cancer patients. “This signature may expose an Achilles’ heel of sarcomatoid kidney cancers that makes them more vulnerable to immunotherapy treatment.our study lays the groundwork for developing future tests to help us better manage this disease, and its implications may also be applicable to other types of kidney cancer.”
To apply and develop the findings from this retrospective genomic analysis, within the next year Roswell Park plans to initiate a prospective study to assess the impact of this gene signature for predicting immunotherapy response in kidney cancer patients who have undergone surgical removal of a kidney tumor.Genomics-guided tool aids immunotherapy selection for advanced kidney cancers
A new tool leveraging genomic data is helping oncologists make more informed decisions about immunotherapy treatment for patients with advanced kidney cancers,according to research published in August 2025. the tool analyzes tumor DNA to predict which patients are most likely to respond to immunotherapy, potentially sparing those who won’t benefit from the treatment’s side effects and costs. https://medicalxpress.com/news/2025-08-genomics-tool-immunotherapy-choices-advanced.html
Understanding Immunotherapy and Kidney Cancer
Kidney cancer, also known as renal cell carcinoma, is a disease in which malignant cells form in the kidneys. Advanced kidney cancer, meaning it has spread to other parts of the body, can be challenging to treat. Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. It effectively works by boosting the body’s natural defenses to recognize and attack cancer cells. However, not all patients respond to immunotherapy, and it can have meaningful side effects.https://www.cancer.gov/types/kidney
How the Genomics-Guided Tool Works
The new tool focuses on analyzing the tumor’s genomic landscape – specifically, the mutations present in the cancer cells. Certain genomic characteristics are associated with a higher or lower likelihood of responding to immunotherapy drugs like checkpoint inhibitors. By identifying these biomarkers, the tool can definitely help predict treatment response.
The tool analyzes factors such as:
Tumor Mutational Burden (TMB): A higher TMB, meaning more mutations, often correlates with a better response to immunotherapy. This is because more mutations can create more neoantigens – abnormal proteins that the immune system can recognize as foreign.https://www.cancer.gov/about-cancer/treatment/immunotherapy/tumor-mutational-burden
Microsatellite Instability (MSI): MSI is a condition where there are changes in the way DNA is copied during cell division.Tumors with high MSI are often more responsive to immunotherapy. https://www.cancer.gov/about-cancer/treatment/immunotherapy/microsatellite-instability
Specific Gene Mutations: Mutations in certain genes can also predict response or resistance to immunotherapy.
Benefits of Personalized Immunotherapy Selection
Using genomic data to guide immunotherapy decisions offers several potential benefits:
Improved Treatment Outcomes: By selecting the right treatment for the right patient, the tool aims to increase the chances of a positive response. Reduced Side Effects: Patients who are unlikely to benefit from immunotherapy can avoid unnecessary exposure to its potentially harmful side effects.
Cost-Effectiveness: Avoiding ineffective treatments can reduce healthcare costs.
* Accelerated Research: The data collected from using this tool can contribute to a better understanding of immunotherapy response and the advancement of even more effective treatments.
Future Directions
Researchers are continuing to refine the tool and explore its potential applications in other types of cancer. Further studies are needed to validate its effectiveness in larger and more diverse patient populations. The ultimate goal is to personalize cancer treatment based on each patient’s unique genomic profile, maximizing the chances of success and improving quality of life.
Disclaimer: This information is for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
Citation: Genomics-guided tool helps guide immunotherapy choices for advanced kidney cancers (2025, August 8) retrieved 8 August 2025 from[https://medicalxpress.com/news/2025-08-genomics-tool-immun