Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists
Abstract
:Simple Summary
Abstract
1. Introduction
2. Intratumoural PRR Ligands and the TME
2.1. TLR Agonists
2.1.1. TLR9
2.1.2. TLR2
2.1.3. TLR3
2.1.4. TLR4
2.1.5. TLR7/8
2.2. STING, RIG-I, or NLR Agonists
2.2.1. RIG-I
2.2.2. STING
2.3. Available Local Antigen Dose—The Missing Ingredient?
3. Concluding Statement
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Intratumoural Agonist | Analogues | PRR Receptors | Notable Cytokines | Effects on APCs | Critical Effector Cells | Beneficial Combinations |
---|---|---|---|---|---|---|
Pam3CSK4 | TLR1 TLR2 | IFN-γ | Limited effects alone | Limited effects alone | Anti-CTLA-4 [33] | |
acGM-1.8 | TLR2 | TNF, IL-12p70 and IFN-γ | Increased M1/M2 macrophage ratio | Increased Teff/Treg ratio | ||
Poly I:C | BO-112 | TLR3 RIG-I | Type I IFN | Dependent on cDC1 | Increased Teff/Treg ratio | Flt3 ligand with anti-PD-L1 mAb and BRAF inhibition [34]; CpG-ODN [35] |
Poly A:U | TLR3 | Type I IFN | Activate cDCs | Increased Teff/Treg ratio and granzyme B-producing CD8+ T cells | ||
LPS | MPL G100 | TLR4 | Type I IFN | Activate cDC1s Increased M1/M2 macrophage ratio | Increased Teff Increased NK cells | Anti-CD40 mAb [36]; anti-PD1 or anti-PD-L1 [37] |
Resiquimod (R848) | TLR7 TLR8 | Type I IFN | Activate pDCs Activation of cDCs Increased M1/M2 macrophage ratio | Increased Teff | ||
Telratolimod | TLR7 TLR8 | Type I IFN | Activate pDCs Activation of cDCs Increased M1/M2 macrophage ratio | Increased Teff | Anti-PD-L1 mAb [29]; anti-PD-1 mAb [38]; anti-CTLA-4 and anti-PD-L1 mAb [39]; anti-OX40 mAb [29] | |
CpG ODN | SD-101 CMP-001 IMO-2125 | TLR9 | Type I IFN | Macrophages responsible for early rejection phase Activate pDCs Accumulation and activation of cDCs Reduced MDSC function | Increased infiltration of antigen-specific T cells Increased NK cells | Anti-CD40 antibody [40]; anti-CTLA4 [41]; anti-OX40 mAb alone [42] or in combination with anti-CTLA-4 [43]; anti-PD-1 mAb alone [44] or in combination with local radiotherapy [45]; metronomic cyclophosphamide [31], doxorubicin [46]; ibrutinib [47]; poly I:C [35]; 3M-052 [48] |
MK461 | RIG-I | Type I IFN | Dependent on T and NK cells | |||
SLR14 | RIG-I | Type I IFN | Phagocytosed by CD11b+ myeloid cells | Increased Teff/Treg ratio | Anti-PD-1 [49] | |
Murine CDNs | DMXAA CDG | STING | Type I IFN | Dependent on cDC1 | Dependent on T cells | Anti-CTLA-4, anti-PD-1 and agonistic anti-CD137 [50]; carboplatin and anti-PD1 [51] |
Synthetic human CDNs | ADU-S100 cGAMP GSK532 | STING | Type I IFN | Activate cDCs | Dependent on CD8+ T cells | VEGFR2 blockade and anti-CTLA-4 or anti-PD1 mAb [52]; anti-PD-1 with anti-CTLA4 [53] |
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Burn, O.K.; Prasit, K.K.; Hermans, I.F. Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists. Cancers 2020, 12, 3824. https://doi.org/10.3390/cancers12123824
Burn OK, Prasit KK, Hermans IF. Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists. Cancers. 2020; 12(12):3824. https://doi.org/10.3390/cancers12123824
Chicago/Turabian StyleBurn, Olivia K., Kef K. Prasit, and Ian F. Hermans. 2020. "Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists" Cancers 12, no. 12: 3824. https://doi.org/10.3390/cancers12123824