The immune checkpoint regulator PD-L1 is highly expressed in aggressive primary prostate cancer
Menée sur une cohorte initiale de 209 patients atteints d'un cancer de la prostate, puis validée sur 611 patients complémentaires, cette étude met en évidence des niveaux élevés d'expression de PD-L1 dans plus de 50% des tumeurs et montre l'association entre ces niveaux élevés et le risque de récidive biochimique
Purpose: Therapies targeting the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway promote anti-tumor immunity and have shown promising results in various tumors. Preliminary data further indicate that immunohistochemically detected PD-L1 may be predictive for anti-PD-1 therapy. So far, no data are available on PD-L1 expression in primary prostate cancer.
Experimental design: Following validation of a monoclonal antibody, immunohistochemical analysis of PD-L1 expression was performed in two independent, well-characterized cohorts of primary prostate cancer patients following radical prostatectomy (RP), and resulting data were correlated to clinicopathological parameters and outcome.
Results: In the training cohort (n=209), 52.2% of cases expressed moderate to high PD-L1 levels, which positively correlated with proliferation (Ki67, p<0.001), Gleason score (p=0.004), and androgen receptor (AR) expression (p<0.001). Furthermore, PD-L1-positivity was prognostic for biochemical recurrence (BCR; p=0.004; HR=2.37 [95%CI=1.32-4.25]. In the test cohort (n=611) moderate to high PD-L1 expression was detected in 61.7% and remained prognostic for BCR in univariate Cox analysis (p=0.011; HR=1.49 [95%CI=1.10-2.02]. The correlation of Ki-67 and AR with PD-L1 expression was confirmed in the test cohort (p<0.001). In multivariate Cox analysis of all patients, PD-L1 was corroborated as independently prognostic for BCR (p=0.007; HR=1.46 [95%CI=1.11-1.92].
Conclusion: We provide first evidence that expression of the therapy target PD-L1 is not only highly prevalent in primary prostate cancer cells but is also an independent indicator of BCR, suggesting a biological relevance in primary tumors. Further studies need to ascertain, if PD-1/PD-L1 targeted therapy might be a treatment option for hormone-naive prostate cancers.
Clinical Cancer Research , résumé, 2015