Florent Petitprez1, Nicola Fossati2, Yann Vano3, Massimo Freschi4, Etienne Becht5, Roberta Lucianò4, Julien Calderaro5, Tiffany Guédet5, Laetitia Lacroix5, Paola M V Rancoita6, Francesco Montorsi7, Wolf Herman Fridman5, Catherine Sautès-Fridman5, Alberto Briganti8, Claudio Doglioni9, Matteo Bellone10. 1. INSERM, UMR_S 1138, Cordeliers Research Center, Team Cancer, Immune Control and Escape, Paris, France; University Paris Descartes Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; UPMC University Paris 6, Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France. 2. Unit of Urology and URI, Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy; NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy. 3. INSERM, UMR_S 1138, Cordeliers Research Center, Team Cancer, Immune Control and Escape, Paris, France; University Paris Descartes Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; UPMC University Paris 6, Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; Department of Medical Oncology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France. 4. NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy; Unit of Pathology, Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy. 5. INSERM, UMR_S 1138, Cordeliers Research Center, Team Cancer, Immune Control and Escape, Paris, France; University Paris Descartes Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; UPMC University Paris 6, Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France. 6. University Centre of Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milan, Italy. 7. Unit of Urology and URI, Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy; NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. 8. Unit of Urology and URI, Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy; NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: briganti.alberto@hsr.it. 9. NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy; Unit of Pathology, Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. 10. NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy; Cellular Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: bellone.matteo@hsr.it.
Abstract
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.
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.
Authors: Anna Sofia Trigos; Anupama Pasam; Patricia Banks; Roslyn Wallace; Christina Guo; Simon Keam; Heather Thorne; Catherine Mitchell; Stephen Lade; David Clouston; Alexander Hakansson; Yang Liu; Benjamin Blyth; Declan Murphy; Nathan Lawrentschuk; Damien Bolton; Daniel Moon; Phil Darcy; Ygal Haupt; Scott G Williams; Elena Castro; David Olmos; David Goode; Paul Neeson; Shahneen Sandhu Journal: J Immunother Cancer Date: 2022-06 Impact factor: 12.469
Authors: Oksana Zavidij; Nicholas J Haradhvala; Tarek H Mouhieddine; Romanos Sklavenitis-Pistofidis; Songjie Cai; Mairead Reidy; Mahshid Rahmat; Abdallah Flaifel; Benjamin Ferland; Nang K Su; Michael P Agius; Jihye Park; Salomon Manier; Mark Bustoros; Daisy Huynh; Marzia Capelletti; Brianna Berrios; Chia-Jen Liu; Meng Xiao He; Esteban Braggio; Rafael Fonseca; Yosef E Maruvka; Jennifer L Guerriero; Melissa Goldman; Eliezer M Van Allen; Steven A McCarroll; Jamil Azzi; Gad Getz; Irene M Ghobrial Journal: Nat Cancer Date: 2020-04-27