4.5 Article

PD-L1 Expression and CD8+ T-cell Infiltrate are Associated with Clinical Progression in Patients with Node-positive Prostate Cancer

Journal

EUROPEAN UROLOGY FOCUS
Volume 5, Issue 2, Pages 192-196

Publisher

ELSEVIER
DOI: 10.1016/j.euf.2017.05.013

Keywords

Prostate cancer; PD-L1; T lymphocytes; B lymphocytes; Lymph node metastasis; Recurrence; Progression; Radical prostatectomy; Biomarker; Immune checkpoint

Funding

  1. IRCCS Ospedale San Raffaele (5x1000)
  2. Associazione Italiana per la Ricerca sul Cancro (IG 2015) [16807]
  3. Hexal AG
  4. Institut National de la Sante et de la Recherche Medicale
  5. University Paris-Descartes
  6. University Pierre et Marie Curie
  7. Institut National du Cancer [2011-1-PLBIO-06-INSERM 6-1, PLBIO09-088-IDF-KROEMER]
  8. Association pour la Recherche sur le Cancer
  9. Cancer Research for Personalized Medicine programme (CARPEM T8)
  10. Labex Immuno-Oncology [LAXE62_9UMRS972 FRIDMAN]
  11. CARPEM doctorate fellowship

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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. (c) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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