Paucity of PD-L1 Expression in Prostate Cancer: Innate and Adaptive Immune Resistance

BACKGROUND: Primary prostate cancers are infiltrated with PD-1 expressing CD8+ T cells. However, in early clinical trials, men with mCRPC did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express PD-L1, the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that PTEN loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 up-regulation - constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. METHODS: Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. RESULTS: In vitro, many prostate cancer cell lines up-regulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. CONCLUSIONS: These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates anti-tumor immune responses in this disease.