Magnitude of PD-1, PD-L1 and T Lymphocyte Expression on Tissue from Castration-Resistant Prostate Adenocarcinoma: An Exploratory Analysis

Magnitude of PD-1, PD-L1 and T Lymphocyte Expression on Tissue from Castration-Resistant Prostate Adenocarcinoma: An Exploratory Analysis

Targeted Oncology, November 2015

26566945

Francesco Massari, Chiara Ciccarese, Anna Caliò, Enrico Munari, Luca Cima, Antonio Benito Porcaro, Giovanni Novella, Walter Artibani, Teodoro Sava, Albino Eccher, Claudio Ghimenton, Francesco Bertoldo, Aldo Scarpa, Nicola Sperandio, Camillo Porta, Vincenzo Bronte, Marco Chilosi, Giuseppe Bogina, Giuseppe Zamboni, Giampaolo Tortora, Hemamali Samaratunga, Guido Martignoni, Matteo Brunelli

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.