Toll-Like Receptors and the Response to Radiotherapy in Solid Tumors: Challenges and Opportunities
Abstract
:1. Introduction
2. Activation and Inhibition of TLRs in Cancer
2.1. TLR1 and TLR2—Pro and Anti-Tumoral Roles
2.2. TLR3—Mostly Anti-Tumoral Effects Mediated by Dendritic Cells and CD8 T Cells
2.3. TLR4—Pro-Tumoral—Cancer Cell Intrinsic Activation
2.4. TLR5—Anti-Tumoral—Action Primarily Mediated by Neutrophils
2.5. TLR7 and TLR8—Primarily Anti-Tumoral
2.6. TLR9—Pro-Tumoral and Anti-Tumoral—Action Mediated through APCs
3. The Effects of Radiation on TLRs
4. Combining Radiotherapy and TLR-Based Therapy
4.1. Radiotherapy and TLR Agonist-Based Therapies: TLR3, TLR7/8 and TLR9
4.2. Radiotherapy and Antagonist-Based Therapies: TLR1, TLR2, TLR4
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Receptor | Ligand | Pro-Tumoral Effect (# of Studies) | Anti-Tumoral Effect (# of Studies) | Contributing Factors |
---|---|---|---|---|
TLR1/2 | BLP | Colorectal (2); Gastric (1); Ovarain (1) | Lung (3); Melanoma (1) | Effects are modulated through cancer-intrinsic mechanisms which vary depending on tumor type |
TLR3 | Poly (I:C) | Esophageal (1); Breast (1); Gastric (1); HNSCC (1) | Lung (6); HNSCC (2); HCC (5); CRC (2); Neuroblastoma (1); Clear cell carcinoma (1); Breast (1); Cervical (1); Prostate (1); Melanoma (1) | Primarily anti-tumorigenic effects that are cancer-intrinsic and/or involve dendritic cells and CD8 T cells. Few correlative and in vitro studies suggest a pro-tumoral effect. |
TLR4 | LPS | Lung (3); Breast (5); PDAC (1) | - | Pro-tumorigenic effect that is primarily cancer-cell intrinsic with limited immune involvement. |
TLR5 | Flagellin | - | Gastric (1); CRC (1); Breast (3); Prostate (1) | Anti-tumorigenic effect mediated through neutrophils (likely N1). |
TLR7/8 | ssRNA | PDAC (1) | Sarcoma (1); PDAC (1); Lung (1); CRC (1); Melanoma (1) | Anti-tumorigenic effect mediated through NK and CD8 T cells and decreasing MDSCs and Tregs |
TLR9 | CpG | PDAC (1) | Melanoma (2); CRC (1); PDAC (2) | Mainly anti-tumorigenic effects mediated through recruitment of cDCs and priming of CTLs |
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Haroun, R.; Naasri, S.; Oweida, A.J. Toll-Like Receptors and the Response to Radiotherapy in Solid Tumors: Challenges and Opportunities. Vaccines 2023, 11, 818. https://doi.org/10.3390/vaccines11040818
Haroun R, Naasri S, Oweida AJ. Toll-Like Receptors and the Response to Radiotherapy in Solid Tumors: Challenges and Opportunities. Vaccines. 2023; 11(4):818. https://doi.org/10.3390/vaccines11040818
Chicago/Turabian StyleHaroun, Ryma, Sahar Naasri, and Ayman J. Oweida. 2023. "Toll-Like Receptors and the Response to Radiotherapy in Solid Tumors: Challenges and Opportunities" Vaccines 11, no. 4: 818. https://doi.org/10.3390/vaccines11040818