Toll-like receptors in prostate infection and cancer between bench and bedside

Authors

  • Guido Gambara,

    1. Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
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  • Paola De Cesaris,

    1. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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  • Cosimo De Nunzio,

    1. Department of Urology, Sant'Andrea Hospital, Rome, Italy
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  • Elio Ziparo,

    1. Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
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  • Andrea Tubaro,

    1. Department of Urology, Sant'Andrea Hospital – Department of Clinical and Experimental Medicine, Sapienza University of Rome, Rome, Italy
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  • Antonio Filippini,

    Corresponding author
    • Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
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  • Anna Riccioli

    1. Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
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Correspondence to: Antonio FILIPPINI, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Histology and Medical Embryology, Sapienza University of Rome, 16 Via Antonio Scarpa, Rome 00161, Italy.

Tel.: +39 0649766585

Fax: +39 064462854

E-mail: antonio.filippini@uniroma1.it

Abstract

Toll-Like receptors (TLRs) are a family of evolutionary conserved transmembrane proteins that recognize highly conserved molecules in pathogens. TLR-expressing cells represent the first line of defence sensing pathogen invasion, triggering innate immune responses and subsequently priming antigen-specific adaptive immunity. In vitro and in vivo studies on experimental cancer models have shown both anti- and pro-tumoural activity of different TLRs in prostate cancer, indicating these receptors as potential targets for cancer therapy. In this review, we highlight the intriguing duplicity of TLR stimulation by pathogens: their protective role in cases of acute infections, and conversely their negative role in favouring hyperplasia and/or cancer onset, in cases of chronic infections. This review focuses on the role of TLRs in the pathophysiology of prostate infection and cancer by exploring the biological bases of the strict relation between TLRs and prostate cancer. In particular, we highlight the debated question of how reliable mutations or deregulated expression of TLRs are as novel diagnostic or prognostic tools for prostate cancer. So far, the anticancer activity of numerous TLR ligands has been evaluated in clinical trials only in organs other than the prostate. Here we review recent clinical trials based on the most promising TLR agonists in oncology, envisaging a potential application also in prostate cancer therapy.

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