gms | German Medical Science

Since prostate cancer is androgen receptor-driven, androgen-deprivation therapy (ADT) remains the standard treatment in advanced disease. Yet, effective treatment remains an unmet medical need due to progression to metastatic castration-resistant prostate cancer (mCRPC) in most advanced cases. While immunotherapy shows promising results in several solid tumors, clinical trials in prostate cancer have been so far disappointing. Most common mechanisms of ADT resistance include androgen receptor (AR) overexpression, and the emergence of ligand-independent AR splice variants (ARv’s), most common of which is ARv7. This study aims to explore the crosstalk between AR-driven prostate cancer cells and T cells. For this, the effect of the secretome of AR- and ARv7-expressing prostate cancer cells on T cells was investigated. LNCaP cells were transduced with AR- or ARv7-encoding lentivirus to generate stable cell lines (LNCaP AR, LNCaP ARv7). Conditioned media (CM) from LNCaP WT, LNCaP AR, and LNCaP ARv7 cell lines was collected and tested on peripheral blood mononuclear cells (PBMCs). Compared to CM of wildtype (WT) LNCaP cells, CM of LNCaP AR and LNCaP ARv7 does not affect TNF-α, CD107a, or Ki-67 expression in CD8+ T cells. Interestingly, CM of LNCaP AR and LNCaP ARv7 reduces IFN-γ expression in CD8 + T cells, compared to CM of WT LNCaP. Proteomics analysis of CM showed a significant upregulation of soluble ULBP2 in the CM of LNCaP AR and ARv7 compared to that of the WT CM. Further functional experiments to confirm the association of ULBP2 in the observed phenotype are ongoing.