Researchers at Northwestern Medicine have identified immune system markers that may help predict which patients respond to BCG bladder cancer therapy and which do not. The findings, published in the Journal of Clinical Investigation, could lead to more personalized treatment approaches for bladder cancer patients.
BCG (Bacillus Calmette-Guérin) therapy is a standard immunotherapy for non-muscle invasive bladder cancer, but it is effective in only about half of patients. Identifying biomarkers that can predict response could spare non-responders from ineffective treatment and its side effects, while allowing responders to continue with a therapy that works.
The study analyzed tumor samples from patients before and after BCG therapy. The researchers found that specific immune cell populations and gene expression patterns were associated with response to treatment. Patients who responded to BCG therapy had higher levels of certain immune cells, including CD8+ T cells and natural killer cells, in their tumors before treatment. Non-responders had a more immunosuppressive tumor microenvironment, with higher levels of regulatory T cells and myeloid-derived suppressor cells.
“Our findings suggest that the immune landscape of the tumor before treatment can determine whether a patient will benefit from BCG,” said a lead researcher. “This could allow us to identify patients who are likely to respond and those who might need alternative therapies.”
The researchers also identified a gene signature that could predict response with high accuracy. This signature includes genes involved in immune activation and antigen presentation. If validated in larger studies, this gene signature could be developed into a clinical test to guide treatment decisions.
Bladder cancer is the sixth most common cancer in the United States, with an estimated 83,000 new cases in 2024. BCG therapy has been the standard of care for high-risk non-muscle invasive bladder cancer for decades, but its efficacy varies widely. The ability to predict response could significantly impact patient outcomes and healthcare costs.
This research adds to a growing body of work on immunotherapy biomarkers. Companies like Calidi Biotherapeutics Inc. (NYSE American: CLDI) are also exploring innovative immunotherapies for cancer. Calidi Biotherapeutics is developing stem cell-based platforms to deliver oncolytic viruses and other immune-modulating agents directly to tumors. Their approach aims to enhance the body's immune response against cancer cells, potentially offering new options for patients who do not respond to existing therapies.
While the Northwestern study is promising, further research is needed to validate the biomarkers and develop a clinically applicable test. The researchers plan to conduct larger prospective studies to confirm their findings and explore the biological mechanisms underlying the differences in immune response.
The study was supported by the National Institutes of Health and the U.S. Department of Veterans Affairs. The findings were published in the Journal of Clinical Investigation.
