San Diego, CA USA (UroToday.com) A very interesting podium presentation was presented in today’s sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I session at the AUA 2016 that described the Immune Profiling of Testicular Germ Cell Tumors and Revealed High Expression of PD-L1 and PD-1. Activation of the immunosuppressive PD-1/PD-L1 (programmed death ligand 1) pathway has been shown to be an important immune surveillance evasion mechanism in solid tumors.
Testicular germ cell tumors (TGCT) have been long recognized to harbor extensive lymphocytic infiltrates, suggesting a dominant role for immune editing in these lesions. The authors evaluated the tumor specific immune microenvironment in TGCTs to determine a potential utility for immune checkpoint blockade therapies in these tumors. The authors profiled the immune infiltrate in TGCT with particular focus on immune checkpoint and T-regulatory cell function. Using validated immunohistochemical stains for PD1 (anti-PD1 antibody "ab52587"), PDL-1 (Cell Signaling, E1L3N, 1:100), FOXP3 (eBioscience, 236A/E7, 1:250) and a double immunostain for CD8 and ki67 (Thermo Scientific, SP16, 1:900 and Invitrogen/Zymed 7B11, 1:900; respectively), applied to TMA sections, they evaluated a retrospectively collected cohort (1995-2008) of 98 TGCT that comprised of 47 seminoma, 14 teratoma, 1 chorioncarcinoma, 13 yolk-sac tumors and 23 embryonal carcinoma. The authors found immunoreactivity for PD-1 and PD-L1 in 96/98 (94%) and 69/98 (70%) respectively.
Notably, PD-L1 expression was predominantly found in infiltrating immune cells and was detected in seminoma and embryonal GCT cells. Positivity for PD-1 correlated with the overall extents of immune infiltrate. FOXP3 positive cells were detected in 87/98 (88%) lesions and a positive correlation between the CD8 positive infiltrate and FOXP3 positive cells was observed.
The extent of proliferating cells T-cells (as determined by CD8 and ki67 double positive immunoreactivity) was associated with PD1 expression (r = 0.41).
The authors conclude that regulatory T-cell infiltrate and PD-1 and PD-L1 expression are common features in germ cell tumors. This may suggests that therapeutic approaches involving immune checkpoint molecule blockade might be beneficial in patients with TGCT.
Presented By: Michael Haffner, MD
Written By: Miki Haifler MD. Fox Chase Cancer Center, Philadelphia, PA. at the 2016 AUA Annual Meeting - May 6 - 10, 2016 – San Diego, California, USA