High-throughput Sequencing Quantitative Analysis of altered genes expression in bladder cancer with anti-PD-1 treatment
Immune-checkpoint blockade (ICB) therapy has profoundly changed the landscape of cancer treatment strategies. Despite its success, resistance remains a significant challenge, with the majority of patients exhibiting non-response to ICB therapies. ICB reinvigorates tumor-specific T cells by interrupting inhibitory signals mediated by checkpoints like PD-1 and CTLA-4, pivotal for the reactivation of their anti-tumor functions. Within the tumor microenvironment, tumor-specific T cells enter a state of dysfunction, making it difficult to generate an effective response to ICB. This study aims to investigate the altered transcriptome in anti-PD-1 responders and non-responders of bladder cancer (BCa) and to uncover the underlying mechanisms of T cell non-responses to ICB. Overall design: To explore T cell dysfunction contributing to ICB resistance in BCa, we developed an immunocompetent spontaneous BCa mouse model. After tumor formation, anti-PD-1 monoclonal antibody was applied to treat BCa. Total RNA from responsive and non-responsive BCa was extracted, and high-throughput sequencing was conducted to investigate the expression profile differences between non-responders and responders.