Researchers at Northwestern Medicine have identified immune system biomarkers that may help predict which patients with bladder cancer will respond to Bacillus Calmette-Guérin (BCG) therapy, according to a study published in the Journal of Clinical Investigation. The findings could lead to personalized treatment strategies, sparing non-responders from ineffective therapy and its side effects while guiding responders toward continued treatment.
Bladder cancer is the sixth most common cancer in the United States, with an estimated 83,000 new cases diagnosed annually. BCG therapy, an immunotherapy that uses a weakened live bacterium to stimulate the immune system to attack cancer cells, is the standard treatment for high-risk non-muscle-invasive bladder cancer. However, up to 40% of patients do not respond to BCG, and there are currently no reliable biomarkers to predict response prior to treatment.
The Northwestern team analyzed tumor samples from bladder cancer patients before and after BCG therapy, using single-cell RNA sequencing and other techniques to identify immune cell populations and gene expression patterns associated with treatment response. They found that patients who responded to BCG had a higher abundance of certain T-cell subtypes and natural killer cells, as well as specific cytokine signaling pathways, compared with non-responders.
“Our study provides a comprehensive immune landscape of bladder cancer and identifies potential biomarkers that could be used to select patients for BCG therapy,” said Dr. Joshua J. Meeks, senior author of the study and professor of urology at Northwestern University Feinberg School of Medicine. “This is a crucial step toward precision medicine in bladder cancer.”
The research is part of a broader effort to refine immunotherapy approaches for cancer. Companies like Calidi Biotherapeutics Inc. (NYSE American: CLDI) are also working to advance immunotherapies, including novel oncolytic virus platforms that could complement BCG therapy. While the Northwestern study focuses on biomarkers, Calidi Biotherapeutics is developing stem cell-based delivery systems for cancer-killing viruses, which may enhance immune responses against tumors.
The identification of predictive biomarkers for BCG response could have significant clinical implications. Patients predicted to be non-responders could be offered alternative treatments, such as radical cystectomy (surgical removal of the bladder) or clinical trials with novel agents, thereby avoiding the toxicity and delay associated with ineffective BCG therapy. Conversely, patients likely to respond could be treated with BCG with greater confidence, potentially reducing the need for aggressive surgery.
“These biomarkers could change how we manage bladder cancer,” said Dr. Meeks. “Instead of a one-size-fits-all approach, we can tailor therapy to each patient’s immune profile.”
Further validation studies are needed before the biomarkers can be used in clinical practice. The Northwestern team plans to test the markers in larger patient cohorts and in prospective trials. If confirmed, the biomarkers could become a routine part of bladder cancer diagnosis and treatment planning, improving outcomes for thousands of patients each year.
