Northwestern Medicine researchers have discovered immune system biomarkers that could help predict which bladder cancer patients will respond to Bacillus Calmette-Guérin (BCG) therapy, according to a study published in the Journal of Clinical Investigation. The findings may enable personalized treatment strategies for patients with non-muscle invasive bladder cancer, the most common form of the disease.
BCG therapy, a form of immunotherapy, has been a standard treatment for high-risk non-muscle invasive bladder cancer for decades. However, up to 40% of patients do not respond to the treatment, and currently there is no reliable way to identify non-responders before therapy begins. The new research, led by Dr. Joshua J. Meeks and colleagues, analyzed tumor samples from patients undergoing BCG therapy and identified specific immune cell signatures that correlated with treatment outcomes.
The study found that tumors from patients who responded to BCG therapy had higher levels of CD8+ T cells and natural killer (NK) cells, along with specific gene expression patterns associated with an active immune microenvironment. In contrast, non-responders had tumors with fewer immune cells and higher expression of genes linked to immune suppression and T cell exhaustion. These biomarkers could potentially be used to stratify patients at diagnosis, allowing those unlikely to benefit from BCG to receive alternative therapies earlier.
“Our findings provide a roadmap for predicting response to BCG therapy and highlight potential targets to improve treatment efficacy,” said Meeks, a professor of urology at Northwestern University Feinberg School of Medicine and a researcher at the Robert H. Lurie Comprehensive Cancer Center. The team plans to validate the biomarkers in larger clinical trials and explore whether combining BCG with other immunotherapies could benefit non-responders.
The study contributes to the growing field of immunotherapy biomarkers. Companies like Calidi Biotherapeutics Inc. (NYSE American: CLDI) are also working to refine immunotherapies for cancer, though their focus is on oncolytic virus platforms. The Northwestern research underscores the importance of understanding tumor-immune interactions in developing precision medicine approaches.
Bladder cancer is the sixth most common cancer in the United States, with an estimated 83,000 new cases diagnosed annually. Non-muscle invasive bladder cancer accounts for about 75% of cases, and BCG therapy remains a cornerstone of treatment despite its variable efficacy. If validated, these biomarkers could transform clinical decision-making, sparing patients from ineffective treatments and reducing healthcare costs.
The findings also have implications for other cancers treated with immunotherapy. The identification of immune cell signatures that predict response could be applied to other tumor types, though further research is needed. The study was supported by the National Cancer Institute and the U.S. Department of Veterans Affairs.
