Prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy are at higher risk of tumor recurrence and receive immediate androgen deprivation therapy (ADT). While approximately 30% of these patients do not experience recurrence, others experience disease recurrence despite ADT, and currently no biomarkers can accurately identify them. We analyzed tumors from 51 patients with node-positive prostate cancer using immunohistochemistry to investigate whether expression of the immune checkpoint ligand PD-L1 by tumor cells or the density of CD8+ or CD20+ cells are associated with clinical progression. Patients with at least 1% PD-L1+ tumor cells had shorter metastasis-free survival than those with PD-L1- tumors (p=0.008, log-rank test). Univariate Cox regression showed that patients with PD-L1+ tumors had almost four times the risk of experiencing distant metastases than those with PD-L1- tumors (hazard ratio 3.90). In addition, we found that PD-L1 expression was significantly associated with CD8+ T-cell density, but not with CD20+ B-cell density. While these results need to be confirmed in larger studies, they show that PD-L1 and CD8 may be used as biomarkers for node-positive patients at high risk of progression. The study also provides a rationale for selecting patients with node-positive PCa who might benefit the most from adjuvant immunotherapies. PATIENT SUMMARY None of the available biomarkers can identify node-positive prostate cancer that will recur after surgery. We found that expression of PD-L1 by tumor cells and a high density of CD8+ T cells in tumor are associated with a higher risk of clinical progression in men with node-positive prostate cancer.