Y chromosome loss in bladder cancer contributes to T cell exhaustion and sensitivity to immune checkpoint blockade [WES]

Loss of the Y chromosome (LOY) is observed in several common cancer types, including 10-40% of bladder cancers, but the clinical and biological significance of this finding is unknown. Through genomic and transcriptomic studies, we report that low LOY gene signature scores correlate with poor prognoses in patients with bladder cancer. We then performed in-depth studies of natural occurring bladder cancer cells with LOY mutants as well as those with targeted deletion of Y chromosome by CRISPR/Cas9. Both Y+ and Y- tumors had similar growth kinetics in vitro, while Y- tumors grew faster than Y+ tumors in immune competent hosts in a T cell-dependent manner Whole Exome sequencing for MB49 parental , MB49 Y chromosome positive and MB49 Y chromosome negative cell lines.