Expression of Programmed Death Ligand 1 (PD-L1) in penile cancer is of prognostic value and associated with HPV status

PD-L1 inhibits T-cell function and prevents tumor eradication. This is facilitated by PD-L1(+) tumor cells and PD-L1(+) immune cells, and can be prevented by anti-PD-1/PD-L1 immunotherapy. In advanced penile cancer there is a need for new therapeutic strategies. This study investigated PD-L1 expression in penile cancers and compared PD-L1 expression with disease-specific survival, lymph-node metastases at diagnosis, and high-risk human papilloma virus (hrHPV) status in a large patient cohort. 213 primary tumors were immunohistochemically stained for PD-L1 and scored for tumor (percentage), stroma (binary) and PD-L1(+) tumor infiltrating macrophages (TIM). Additionally, PD-L1(+) tumors were scored for expression pattern: diffuse or predominantly present at tumor-stroma margin. Staining was successful in 200 tumors. 75% were hrHPV(-). Median follow-up was 62 months. Of 200 tumors, 96 (48%) were PD-L1(+) (scored ≥1%), of which 59 (62%) had a marginal expression pattern and 79 (82%) were hrHPV(-) (p=0.03). Compared to PD-L1(-) tumors, the PD-L1 expression patterns each had different prognostic values, in the whole cohort as well as in the hrHPV(-) subgroup. In multivariable analyses, marginal expression pattern was associated with absence of lymph-node metastases (OR 0.4), while diffuse expression was associated with poor survival (HR 2.58). These results were more prominent in the hrHPV(-) subgroup (OR 0.25 and HR 3.92, respectively). PD-L1 was expressed in 48% of penile carcinomas, and mainly in HPV(-) tumors. Pattern of expression was a prognostic factor as marginal expression was associated with absence of lymph-node metastases, and a diffuse expression with poor survival