Abstract
Prostate cancer is the second most common cancer in men, for which there are no reliable biomarkers or targeted therapies. Here we demonstrate that elevated levels of Delta 133TP53 beta isoform characterize prostate cancers with immune cell infiltration, particularly T cells and CD163+ macrophages. These cancers are associated with shorter progression-free survival, Gleason scores >= 7, and an immunosuppressive environment defined by a higher proportion of PD-1, PD-L1 and colony-stimulating factor 1 receptor (CSF1R) positive cells. Consistent with this, RNA-seq of tumours showed enrichment for pathways associated with immune signalling and cell migration. We further show a role for hypoxia and wild-type p53 in upregulating Delta 133TP53 levels. Finally, AUC analysis showed that Delta 133TP53 beta expression level alone predicted aggressive disease with 88% accuracy. Our data identify Delta 133TP53 beta as a highly accurate prognostic factor for aggressive prostate cancer.