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Updated: May 12, 2026
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Toll-like receptors in prostate infection and cancer between bench and bedside
Guido Gambara1, Paola De Cesaris, Cosimo De Nunzio
1Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
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.
Insights
Toll-Like Receptors (TLRs) play a dual role in prostate cancer, offering protection during acute infections but potentially promoting cancer during chronic infections. Their complex involvement suggests new therapeutic and diagnostic strategies for prostate cancer.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Toll-Like Receptors (TLRs) are key sensors of pathogen invasion, initiating innate and adaptive immune responses.
- TLRs exhibit dual roles in prostate cancer, with both anti- and pro-tumoural effects observed in experimental models.
- The role of TLRs in prostate pathophysiology, particularly in infection and cancer development, requires further elucidation.
Purpose of the Study:
- To review the complex role of Toll-Like Receptors (TLRs) in prostate cancer pathophysiology.
- To explore the biological basis linking TLRs and prostate cancer.
- To evaluate the potential of TLR agonists as therapeutic agents for prostate cancer.
Main Methods:
- Review of in vitro and in vivo studies on TLRs in experimental prostate cancer models.
- Analysis of the duplicity of TLR stimulation in acute versus chronic infections.
- Examination of clinical trials involving TLR agonists in oncology.
Main Results:
- TLRs can have both protective and detrimental effects in prostate cancer, depending on the context of infection.
- Mutations or altered expression of TLRs are being investigated as potential diagnostic and prognostic markers.
- Clinical trials with TLR agonists show promise in other cancers, suggesting potential for prostate cancer therapy.
Conclusions:
- TLRs are critically involved in prostate cancer development and progression.
- Further research is needed to clarify the diagnostic and prognostic value of TLRs in prostate cancer.
- TLR agonists represent a promising avenue for novel prostate cancer therapies.
