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

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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.

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Acknowledgments

Internal funding, Department of Pathology and Diagnostics, Anatomic Pathology, University of Verona (MB, FUR 2013).

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Authors and Affiliations

  1. Medical Oncology, University and Hospital Trust, Verona, Italy

    Francesco Massari, Chiara Ciccarese, Teodoro Sava & Giampaolo Tortora

  2. Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust, Verona, Italy

    Anna Caliò, Enrico Munari, Luca Cima, Albino Eccher, Claudio Ghimenton, Aldo Scarpa, Marco Chilosi, Guido Martignoni & Matteo Brunelli

  3. Urologic Clinic, University and Hospital Trust, Verona, Italy

    Antonio Benito Porcaro, Giovanni Novella & Walter Artibani

  4. Internal Medicine, University and Hospital Trust, Verona, Italy

    Francesco Bertoldo

  5. ARC-NET Applied Research Centre, University of Verona, Verona, Italy

    Aldo Scarpa & Nicola Sperandio

  6. Medical Oncology, IRCCS Foundation, University and Hospital Trust, Pavia, Italy

    Camillo Porta

  7. Department of Pathology and Diagnostics, Immunology, University and Hospital Trust, Verona, Italy

    Vincenzo Bronte

  8. Anatomic Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy

    Giuseppe Bogina & Giuseppe Zamboni

  9. Deparment of Pathology, University of Queensland, Brisbane, Australia

    Hemamali Samaratunga

  10. Department of Pathology and Diagnostics, University of Verona, FISH Lab; P.le. L.A. Scuro n. 10, 37134, Verona, Italy

    Matteo Brunelli

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  1. Francesco Massari
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Corresponding author

Correspondence to Matteo Brunelli.

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MB, AE, LC, FM, GM, MC, AS, CC, HS, NS, EM, AC, GB,GT, TS, CG, AC, WA, AP, CP, and GN declare no conflict of interest.

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Massari, F., Ciccarese, C., Caliò, A. et al. Magnitude of PD-1, PD-L1 and T Lymphocyte Expression on Tissue from Castration-Resistant Prostate Adenocarcinoma: An Exploratory Analysis. Targ Oncol 11, 345–351 (2016). https://doi.org/10.1007/s11523-015-0396-3

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