title: Magnitude of PD-1, PD-L1 and T Lymphocyte Expression on Tissue from Castration-Resistant Prostate Adenocarcinoma: An Exploratory Analysis.
abstract: Recent therapeutic strategies for castration-resistant prostate cancer have focused on immunomodulation, especially the PD-1/PD-L1 pathway related to tumor-infiltrating lymphocytes. Few cases of castration-resistant prostate adenocarcinoma have been tested simultaneously for PD-1, PD-L1 and T lymphocytes in cancerous tissue. We quantified the PD-1/PD-L1 immune pathway and T lymphocyte infiltrates in a series of patients with castrate-resistant prostate adenocarcinoma.
  
  
  
  Expression of PD-1, PD-L1, CD3 and FOXP3 was identified in tissue microarrays, with five tissue spots per patient from 16 patients over at least 5 years of follow-up. Two scores were defined. The first described the percentage of PD-1-positive T lymphocytes (CD3+): negative (0), <5 %; low (1+), 5-30 %; high (2+), >30 %. The second described PD-L1 staining intensity: 0 (no signal), 1+ (light signal), 2+ (high signal) in >50 % of neoplastic cells.
  
  
  
  Tumor-infiltrating T lymphocytes (CD3+) were seen in 11/16 cases (69 %). Nine of 16 cases expressed PD-1 (56 %), among which 19 % were scored 2+. Eight of 16 cases expressed PD-L1 (50 %), with 19 % scored as strong 2+. The subgroup with high PD1/PD-L1 also exhibited FOXP3 expression.
  
  
  
  Approximately 19 % of patients in our series showed simultaneous high PD-1/PD-L1 immunoscores, and were the best candidates for receiving targeted anti-PD-1/PD-L1 immunotherapy, as determined using a tissue based rationale.
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caliò
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cima
authors.affiliation: Urologic Clinic, University and Hospital Trust, Verona, Italy.
authors.forename: Antonio Benito
authors.initials: AB
authors.lastname: Porcaro
authors.affiliation: Urologic Clinic, University and Hospital Trust, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Novella
authors.affiliation: Urologic Clinic, University and Hospital Trust, Verona, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Artibani
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Sava
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Eccher
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.affiliation: Internal Medicine, University and Hospital Trust, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoldo
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.|ARC-NET Applied Research Centre, University of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: ARC-NET Applied Research Centre, University of Verona, Verona, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Sperandio
authors.affiliation: Medical Oncology, IRCCS Foundation, University and Hospital Trust, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Department of Pathology and Diagnostics, Immunology, University and Hospital Trust, Verona, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.affiliation: Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.affiliation: Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Deparment of Pathology, University of Queensland, Brisbane, Australia.
authors.forename: Hemamali
authors.initials: H
authors.lastname: Samaratunga
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy. matteo.brunelli@univr.it.|Department of Pathology and Diagnostics, University of Verona, FISH Lab; P.le. L.A. Scuro n. 10, 37134, Verona, Italy. matteo.brunelli@univr.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D061026:Programmed Cell Death 1 Receptor