Bladder Cancer Response to Immunotherapy Informed by Expression Profiles

NEW YORK (GenomeWeb) – New research suggests that stromal cells in the tumor microenvironment may interfere with immune system’s efforts to combat bladder cancer in patients treated with anti-PD-1 immunotherapy.

Using urothelial cancer data from the Cancer Genome Atlas project, patient xenografts models, and gene expression data for metastatic urothelial cancer patients treated with the PD-1 inhibitor nivolumab, researchers from the Icahn School of Medicine at Mount Sinai, the Mount Sinai spinout Sema4, and elsewhere found that the presence of infiltrating T-cells — the mark of ‘hot’ tumors — seemed to bode well for tumor response to the PD-1 inhibitor nivolumab, while a related epithelial-mesenchymal transition (EMT) expression signature did not.

Instead, the team reported today in Nature Communications, a rise in the EMT signature and expression of non-hematopoietic stromal cell genes dialed down the benefits of T-cell infiltration — potentially through immune exclusion from the tumor — leading to poorer response to nivolumab, and survival times in patients with chemotherapy-resistant metastatic urothelial cancer.

“Some bladder cancers may not respond to immunotherapy, even though the body has developed an immune response against them, because the T-cells are prevented from reaching the tumor by stromal cells that create an inhospitable ‘neighborhood,'”

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