Francesco Massari1, Chiara Ciccarese1, Anna Caliò2, Enrico Munari2, Luca Cima2, Antonio Benito Porcaro3, Giovanni Novella3, Walter Artibani3, Teodoro Sava1, Albino Eccher2, Claudio Ghimenton2, Francesco Bertoldo4, Aldo Scarpa2,5, Nicola Sperandio5, Camillo Porta6, Vincenzo Bronte7, Marco Chilosi2, Giuseppe Bogina8, Giuseppe Zamboni8, Giampaolo Tortora1, Hemamali Samaratunga9, Guido Martignoni2, Matteo Brunelli10,11. 1. Medical Oncology, University and Hospital Trust, Verona, Italy. 2. Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy. 3. Urologic Clinic, University and Hospital Trust, Verona, Italy. 4. Internal Medicine, University and Hospital Trust, Verona, Italy. 5. ARC-NET Applied Research Centre, University of Verona, Verona, Italy. 6. Medical Oncology, IRCCS Foundation, University and Hospital Trust, Pavia, Italy. 7. Department of Pathology and Diagnostics, Immunology, University and Hospital Trust, Verona, Italy. 8. Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy. 9. Deparment of Pathology, University of Queensland, Brisbane, Australia. 10. Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy. matteo.brunelli@univr.it. 11. Department of Pathology and Diagnostics, University of Verona, FISH Lab; P.le. L.A. Scuro n. 10, 37134, Verona, Italy. matteo.brunelli@univr.it.
Abstract
BACKGROUND AND AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIM: 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. PATIENTS AND METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
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