Researchers at Northwestern Medicine have identified immune system markers that may help predict which patients respond to BCG therapy for bladder cancer and which do not. The findings, published in the Journal of Clinical Investigation, could lead to more personalized treatment approaches for non-muscle invasive bladder cancer, the most common form of the disease.
BCG (Bacillus Calmette-Guérin) therapy is a standard immunotherapy for early-stage bladder cancer, but it fails in about 30–40% of patients. Currently, doctors have no reliable way to predict who will benefit. The Northwestern team analyzed tumor samples from patients before and after BCG treatment, focusing on immune cell activity. They discovered that specific patterns of immune markers, including certain types of T cells and cytokine levels, correlated with treatment success.
“Our study reveals that the immune microenvironment of the tumor before treatment can dictate whether a patient will respond to BCG,” said Dr. Joshua Meeks, senior author and associate professor of urology at Northwestern University Feinberg School of Medicine. “These biomarkers could help us identify non-responders early and consider alternative therapies.”
The research involved 50 patients and used advanced techniques such as single-cell RNA sequencing and multiplex immunofluorescence. Patients who responded well to BCG had higher levels of CD8+ T cells and specific immune checkpoint molecules like PD-1 and LAG-3 before treatment. In contrast, non-responders had more exhausted T cells and immunosuppressive myeloid cells.
“This is a significant step toward precision medicine in bladder cancer,” said Dr. Meeks. “If validated in larger trials, these biomarkers could be integrated into clinical practice to guide therapy decisions.”
The implications extend beyond bladder cancer. The study highlights how the immune system’s state influences immunotherapy outcomes, a concept relevant to many cancers. Companies like Calidi Biotherapeutics Inc. (NYSE American: CLDI) are also advancing immunotherapies, including novel approaches to enhance BCG efficacy.
Bladder cancer is the sixth most common cancer in the U.S., with over 80,000 new cases expected this year. Non-muscle invasive bladder cancer is treated with transurethral resection followed by BCG instillations. For patients who fail BCG, options are limited to more aggressive treatments like cystectomy (bladder removal).
The Northwestern team plans to validate their findings in a larger multicenter trial. They also aim to develop a simple blood test to measure these biomarkers, making the approach more accessible. “Our goal is to spare patients from ineffective treatments and their side effects while improving outcomes,” said Dr. Meeks.
This research was funded by the National Institutes of Health and the Department of Defense. The study was published online ahead of print in the Journal of Clinical Investigation.
