Toll-like receptor 3: a double-edged sword
Abstract The discovery of Toll-like receptors (TLRs) and their role in dendritic cells earned the Nobel Prize for 2011 because TLRs profoundly enhanced our understanding of the immune system. Specifically, TLR3 is located within the endosomal compartments of dendritic cells and plays a crucial role...
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BMC
2025-02-01
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| Series: | Biomarker Research |
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| Online Access: | https://doi.org/10.1186/s40364-025-00739-5 |
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| author | Marvin L Hsieh Daisuke Nishizaki Jacob J Adashek Shumei Kato Razelle Kurzrock |
| author_facet | Marvin L Hsieh Daisuke Nishizaki Jacob J Adashek Shumei Kato Razelle Kurzrock |
| author_sort | Marvin L Hsieh |
| collection | DOAJ |
| description | Abstract The discovery of Toll-like receptors (TLRs) and their role in dendritic cells earned the Nobel Prize for 2011 because TLRs profoundly enhanced our understanding of the immune system. Specifically, TLR3 is located within the endosomal compartments of dendritic cells and plays a crucial role in the immune response by acting as a pattern recognition receptor that detects both exogenous (viral) and endogenous (mammalian) double-stranded RNA. However, TLR3 activation is a double-edged sword in various immune-mediated diseases. On one hand, it can enhance anti-viral defenses and promote pathogen clearance, contributing to host protection. On the other hand, excessive or dysregulated TLR3 signaling can lead to chronic inflammation and tissue damage, exacerbating conditions such as autoimmune diseases, chronic viral infections, and cancer. In cancer, TLR3 expression has been linked to both favorable and poor prognoses, though the underlying mechanisms remain unclear. Recent clinical and preclinical advances have explored the use of TLR3 agonists in cancer immunotherapy, attempting to capitalize on their potential to enhance anti-tumor responses. The dual role of TLR3 highlights its complexity as a therapeutic target, necessitating careful modulation to maximize its protective effects while minimizing potential pathological consequences. In this review, we explore the intricate roles of TLR3 in immune responses across different disease contexts, including cancer, infections, autoimmune disorders, and allergies, highlighting both its protective and detrimental effects in these disorders, as well as progress in developing TLR3 agonists as part of the immunotherapy landscape. |
| format | Article |
| id | doaj-art-8e332f01f10d4731be45f110221112a3 |
| institution | DOAJ |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Biomarker Research |
| spelling | doaj-art-8e332f01f10d4731be45f110221112a32025-08-20T03:03:50ZengBMCBiomarker Research2050-77712025-02-0113111410.1186/s40364-025-00739-5Toll-like receptor 3: a double-edged swordMarvin L Hsieh0Daisuke Nishizaki1Jacob J Adashek2Shumei Kato3Razelle Kurzrock4Medical College of WisconsinMoores Cancer Center, University of California San DiegoDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins HospitalMoores Cancer Center, University of California San DiegoMedical College of WisconsinAbstract The discovery of Toll-like receptors (TLRs) and their role in dendritic cells earned the Nobel Prize for 2011 because TLRs profoundly enhanced our understanding of the immune system. Specifically, TLR3 is located within the endosomal compartments of dendritic cells and plays a crucial role in the immune response by acting as a pattern recognition receptor that detects both exogenous (viral) and endogenous (mammalian) double-stranded RNA. However, TLR3 activation is a double-edged sword in various immune-mediated diseases. On one hand, it can enhance anti-viral defenses and promote pathogen clearance, contributing to host protection. On the other hand, excessive or dysregulated TLR3 signaling can lead to chronic inflammation and tissue damage, exacerbating conditions such as autoimmune diseases, chronic viral infections, and cancer. In cancer, TLR3 expression has been linked to both favorable and poor prognoses, though the underlying mechanisms remain unclear. Recent clinical and preclinical advances have explored the use of TLR3 agonists in cancer immunotherapy, attempting to capitalize on their potential to enhance anti-tumor responses. The dual role of TLR3 highlights its complexity as a therapeutic target, necessitating careful modulation to maximize its protective effects while minimizing potential pathological consequences. In this review, we explore the intricate roles of TLR3 in immune responses across different disease contexts, including cancer, infections, autoimmune disorders, and allergies, highlighting both its protective and detrimental effects in these disorders, as well as progress in developing TLR3 agonists as part of the immunotherapy landscape.https://doi.org/10.1186/s40364-025-00739-5Toll-like receptor 3 (TLR3)TLR3 agonistCancerImmunotherapyViral infectionAutoimmune disease |
| spellingShingle | Marvin L Hsieh Daisuke Nishizaki Jacob J Adashek Shumei Kato Razelle Kurzrock Toll-like receptor 3: a double-edged sword Biomarker Research Toll-like receptor 3 (TLR3) TLR3 agonist Cancer Immunotherapy Viral infection Autoimmune disease |
| title | Toll-like receptor 3: a double-edged sword |
| title_full | Toll-like receptor 3: a double-edged sword |
| title_fullStr | Toll-like receptor 3: a double-edged sword |
| title_full_unstemmed | Toll-like receptor 3: a double-edged sword |
| title_short | Toll-like receptor 3: a double-edged sword |
| title_sort | toll like receptor 3 a double edged sword |
| topic | Toll-like receptor 3 (TLR3) TLR3 agonist Cancer Immunotherapy Viral infection Autoimmune disease |
| url | https://doi.org/10.1186/s40364-025-00739-5 |
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