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/PDL1 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/PDL1 immunotherapy, as determined using a tissue based rationale.

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

Ciccarese, Chiara;Calio', Anna;MUNARI, Enrico;CIMA, Luca;PORCARO, Antonio Benito;ARTIBANI, Walter;ECCHER, Albino;BERTOLDO, Francesco;SCARPA, Aldo;Sperandio, Nicola;Bronte, Vincenzo;CHILOSI, Marco;ZAMBONI, Giuseppe;TORTORA, GIAMPAOLO;MARTIGNONI, Guido;BRUNELLI, Matteo
2016

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/PDL1 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/PDL1 immunotherapy, as determined using a tissue based rationale.
Prostate Adenocarcinoma, tumor-infiltrating lymphocytes, PD-1/PD-L1, T Lymphocyte Expression
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/929632
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