Spatiotemporal dynamic evolution of the tumor microenvironment during neoadjuvant immunotherapy for bladder cancer.

In a multicenter real-world cohort of 606 bladder cancer (BLCA) patients, neoadjuvant immunotherapy is linked to dynamic TME evolution, including immunotherapy resistance marked by SERPINH1 and an excluded immune phenotype.

• Why it matters: Resistance and residual disease after neoadjuvant immunotherapy remain poorly characterized in space and time, limiting how clinicians can tailor combination strategies for BLCA.
• What they did: The study profiled BLCA tumor microenvironment samples before and after neoadjuvant immunotherapy (n = 606), distinguishing epithelial differentiation into sensitivity versus resistance and mapping myeloid barrier effects.
• The result: It identifies an immunotherapy-induced tumor-myeloid barrier associated with excluded immune phenotypes and resistance, with T cell terminal exhaustion and senescent inflammatory cancer-associated fibroblasts linked to resistant residual lesions.

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