Molecular Repolarisation of Tumour-Associated Macrophages
Abstract
:1. Introduction
2. Macrophages in Tumourigenesis
3. Targeting Tumour-Associated Macrophages in the Tumour Microenvironment
3.1. TLR Agonists
3.2. Cytokines
3.3. Antibodies
3.4. RNAs
3.5. Small Molecules
3.6. Others
4. Conclusion
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Molecule | Target | Signalling Pathway | Type of Study | Reference | Comments |
---|---|---|---|---|---|
TLR Agonists | |||||
Poly I:C | TLR3 | NFκβ | In vitro and in vivo | [53] | |
Cationic polymers PEI/ C-dextran | TLR4 | NFκβ and IRF3 | In vitro and in vivo | [52] | |
Mycobacterium idicus pranii | TLR4 | NFκβ and AP-1/MAPK P38 | In vivo | [51] | Studied in combination with DTA-1 |
pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) | TLR4 | NFκβ and IRF3 | In vitro and in vivo | [47,48,49,50] | Approved for advanced lung cancer |
Let-7b microRNA mimic | TLR7 and anti-IL10 | NFκβ and IRF7 | In vivo | [55] | Administered in a MRC1-targeted nanoparticle |
Resiquimod (R848) | TLR7/8 | NFκβ and IRF7 | In vitro and In vivo | [56] | Administered in a β-cyclodextrin nanoparticle |
Motolimod | TLR8 | NFκβ | In vivo and phase I/II clinical trials | [59,60,80] | |
CpG motifs | TLR9 | NFκβ and AP-1 | In vivo | [62,63,64] | |
Hyaluronic acid | TLR-2 or TLR-4 | NFκB or IRF3 | In vivo | [66] | |
Cytokines | |||||
CSF2 | CSF2 receptor | JAK/STAT3/5, MAPK, NFκβ, and PI3K | In vivo | [75,76] | Studied in combination with 4-IPP |
IL12 | IL12 receptor | JAK2/STAT4 | In vivo | [74,77] | Administered in a poly(β-amino ester) nanoparticle |
IFNγ | IFNγ receptor | STAT1 | In vitro | [78] | Administered as a chitosan/poly(γ-glutamic acid) nanoparticle |
TRAIL | TRAIL receptor 1 | NFκβ and ERK1/2 | In vitro | [79] | |
Antibodies | |||||
Anti-CSF1 | CSF1 | NFκβ, ERK1/2 and miR21 | In vivo | [81] | |
Anti-LILRB2 | LILRB2 receptor | NFκβ, Erk1/2 and Blocks Akt/STAT6 | In vitro and in vivo | [82] | |
Anti-MARCO | MARCO | FcγRIIB | In vivo | [83] | |
Anti-CD40 | CD40 | NFκβ, ERK1/2 and P38 MAPK | In vivo | [64] | Studied in combination with CpG-ODN |
Anti-IL10 receptor | IL10Rα | Blocks Akt/STAT3 | in vivo | [63] | Studied in combination with CpG-ODN and CCL16 |
Anti-phosphatidylserine | Phosphatidylserine | FcγRII/III | In vivo and phase I/II/III clinical trials | [84,85,86,87] | |
Anti-TREM-1 | TREM-1 | TREM-1/DAP12/Syk | In vitro | [88] | |
Anti-VEGFR-2 | VEGF receptor 2 | Decreased hypoxia sensing | In vivo | [89] | |
Bispecific anti-angiopoietin-2 anti-VEGF-A antibody | Angiopoietin-2 and VEGF-A | Decreased hypoxia sensing | In vivo | [90] | |
RNAs | |||||
miR155/miR125b2 | TNFα/SOCS1/IRF4 | Enhances TNFα translation and blocks SOCS1 and IRF4 | In vitro | [91,92] | Administered in a hyaluronic acid-based nanoparticle |
IκBα siRNA | IκBα | NFκβ | In vitro | [93] | Administered in a mannosylated nanoparticle |
MyD88/TNF mRNA in S. cerevisae | MYD88/TNF receptor | NFκβ and AP-1 | In vitro | [94] | Empty S. cerevisae also activates macrophages |
Small Molecules | |||||
NS-398 | COX2 inhibitor | Blocks PI3K/Akt | In vivo | [95] | |
Etodolac | COX2 inhibitor | Blocks PI3K/Akt | In vivo | [96] | |
Celecoxib | COX2 inhibitor | Blocks PI3K/Akt | In vivo | [97] | |
DMXAA | STING-agonist | TBK1/NFκβ | In vivo | [98] | |
2‘3‘-cGAMP | STING-agonist | TBK1/NFκβ | In vitro | [98] | |
Pexidartinib | CSF1R-inhibitor | STAT3, IRF4 | In vivo | [99,100] | |
BLZ945 | CSF1R-inhibitor | STAT3, IRF4 | In vivo | [101] | |
Ibrutinib | BTK inhibitor | Blocks BTK | In vitro | [102] | Approved for leukemia |
TG100-115 | PI3Kγ inhibitor | Blocks PI3Kγ | In vitro | [102] | |
HS-1793 | HIF1 antagonist | JAK/STAT1 | In vitro | [103,104] | |
Vorinostat | HDAC inhibitor | HDAC2 | In vivo | [105,106,107] | Administered in a redox-responsive nanoparticle |
Sorafenib | Tyrosine kinase inhibitor | Blocks Akt/STAT6 | In vivo | [108,109,110] | Approved for advanced kidney cancer |
Sunitinib | Tyrosine kinase inhibitor | Blocks STAT3 | In vivo | [111] | Studied in combination with anti-GITR, approved for renal and GI cancers |
Baicalin | Unknown | RelB/P52 | In vivo | [112] | |
Chlorogenic acid | Unknown | Activates STAT1 and blocks STAT6 | in vivo | [113] | |
Emodin | Unknown | Blocks Akt/STAT6 | In vivo | [114,115] | |
Hydrazinocurcumin | Unknown | Blocks STAT3 | In vivo | [116] | |
CDDO-Me | Unknown | Unknown | In vivo | [117] | |
Dopamine | Dopamine receptor 2 | Unknown | In vivo | [118] | |
CuNG | ROS generation | MAPK P38, ERK1/2, NFκβ and AP-1 | In vivo | [119,120] | |
Zoledronic acid | Unknown | NFκβ | In vivo | [121,122,123] | Approved for osteoporosis and bone metastases |
Metformin | Unknown | AMPK/NFκβ | In vivo | [124,125,126] | |
Chloroquine | Unknown | NFκβ, P38 MAPK and TFEB | In vivo | [127,128] | |
Others | |||||
Histidine-rich glycoprotein | PIGF | Unknown | In vivo | [129] | |
β-Glucan | Dectin-1 | Erk1/2 | In vivo | [130] |
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Van Dalen, F.J.; Van Stevendaal, M.H.M.E.; Fennemann, F.L.; Verdoes, M.; Ilina, O. Molecular Repolarisation of Tumour-Associated Macrophages. Molecules 2019, 24, 9. https://doi.org/10.3390/molecules24010009
Van Dalen FJ, Van Stevendaal MHME, Fennemann FL, Verdoes M, Ilina O. Molecular Repolarisation of Tumour-Associated Macrophages. Molecules. 2019; 24(1):9. https://doi.org/10.3390/molecules24010009
Chicago/Turabian StyleVan Dalen, Floris J., Marleen H. M. E. Van Stevendaal, Felix L. Fennemann, Martijn Verdoes, and Olga Ilina. 2019. "Molecular Repolarisation of Tumour-Associated Macrophages" Molecules 24, no. 1: 9. https://doi.org/10.3390/molecules24010009
APA StyleVan Dalen, F. J., Van Stevendaal, M. H. M. E., Fennemann, F. L., Verdoes, M., & Ilina, O. (2019). Molecular Repolarisation of Tumour-Associated Macrophages. Molecules, 24(1), 9. https://doi.org/10.3390/molecules24010009