<p>Non-muscle invasive bladder cancer (NMIBC) represents 70–80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guerin (BCG) remains a cornerstone treatment for intermediate- and high-risk NMIBC to prevent disease recurrence and progression. However, a significant number of patients experience recurrence after their first course of BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing (scRNA-Seq) on freshly collected NMIBC samples, distinguishing between those naive to BCG treatment and those that recurred post-BCG treatment. We observed a clear activation of inflammatory pathways across cell types during recurrence, but these were not associated with canonical immune checkpoint or T cell exhaustion phenotypes. Analysis of cell-to-cell communication revealed enhanced interactions between T cells and urothelial cells in BCG-recurrence, predominantly modulated by <a href="https://www.ncbi.nlm.nih.gov/gene/923">CD6</a> and activated leukocyte cell adhesion molecule (<a href="https://www.ncbi.nlm.nih.gov/gene/214">ALCAM</a>). Furthermore, we found CD6hi T cells to be immunosuppressed and enriched in recurrent samples, suggesting a potential role for CD6 as an immune evasion signal in NMIBC.</p>

Single Cell RNA-Sequencing of BCG Naive and Recurrent Non-Muscle Invasive Bladder Cancer Reveals a CD6/ALCAM-Mediated Immune-Suppressive Pathway

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