MEMORY B cells were associated with improved Bacillus Calmette Guérin (BCG) response and longer recurrence free survival in patients with non-muscle invasive bladder cancer, suggesting a potential role for immune biomarkers in guiding treatment decisions.
Researchers found that greater infiltration of tumour infiltrating memory B cells and the presence of mature tertiary lymphoid structures before treatment were linked with superior clinical outcomes following BCG therapy.
The study investigated whether tumour infiltrating memory B cells and tertiary lymphoid structures were associated with response to intravesical BCG in patients with intermediate or high risk non muscle invasive bladder cancer.
Researchers first analysed RNA sequencing data from a discovery cohort using immune cell deconvolution to identify immune cell populations linked with treatment response. Findings were then validated in an independent cohort of 79 patients who received BCG. Pretreatment transurethral resection of bladder tumour specimens was examined using haematoxylin and eosin staining alongside multiplex immunohistochemistry to quantify memory B cell infiltration and tertiary lymphoid structure characteristics.
Pretreatment intratumoural memory B cell abundance was significantly higher in patients who responded to BCG than in non-responders (P=0.0009). Likewise, tertiary lymphoid structure density was greater among responders (P=0.0026).
Exploratory analyses included paired tumour samples from 16 patients who experienced disease recurrence following BCG treatment. Recurrent tumours demonstrated lower levels of memory B cells than pretreatment samples (P=0.0250), together with a numerical increase in primary follicle like tertiary lymphoid structures.
Higher proportions of memory B cells and the presence of secondary follicle like tertiary lymphoid structures were associated with longer recurrence free survival. The strongest clinical outcomes were observed when memory B cells were spatially embedded within secondary follicle like tertiary lymphoid structures, highlighting the potential importance of immune cell organisation as well as abundance.
Multivariable analyses identified T1 stage, high memory B cell infiltration, and the presence of secondary follicle like tertiary lymphoid structures as independent predictors of recurrence free survival.
The findings suggested that enrichment of memory B cells within mature tertiary lymphoid structures before treatment was associated with greater responsiveness to BCG and improved long-term outcomes. These immune features may serve as candidate biomarkers to identify patients most likely to benefit from BCG therapy and could help refine risk stratification in non-muscle invasive bladder cancer.
Reference
Wang H et al. Memory B cells in mature follicle-like tertiary lymphoid structures predict BCG response in non-muscle-invasive bladder cancer. Sci Rep. 2026; https://doi.org/10.1038/s41598-026-60910-2.
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