Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics

Kaur, Arvinder; Baldwin, Jeremy; Brar, Deshkanwar; Salunke, Deepak B.; Petrovsky, Nikolai

doi:10.1016/j.cbpa.2022.102172

Cited by 86 publications

(63 citation statements)

References 146 publications

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“…These glycans participated in hTLR2, but not TLR4, signalling, since their removal with α-mannosidase partially abrogated the T. cruzi lysate-induced hTLR2 signalling. Both TLR2 and TLR4 are expressed on the surface of innate myeloid cells, such as macrophages and dendritic cells, but also endothelial and epithelial cells, and are key initiators of the innate anti-tumour immune response [ 39 ]. In particular, TLR2 mainly interacts with lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Freire

Landeira

Giacomini

et al. 2022

IJMS

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Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.

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Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Freire

Landeira

Giacomini

et al. 2022

IJMS

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show abstract

“…TLR3, TLR7, TLR8 and TIRAP were significantly upregulated in this study. In mammals, TLR3, TLR7 and TLR8, located in intracellular vesicles, are critical receptors for the recognition of viral nucleic acids in the antiviral response ( 64 ). TLR7 was upregulated in both head kidney and spleen within 48 h after tongue sole infection with Pseudomonas fluorescence , and knockdown of TLR7 resulted in significantly higher bacterial load in tissues than in control ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Splenic protection network revealed by transcriptome analysis in inactivated vaccine-immunized flounder (Paralichthys olivaceus) against Edwardsiella tarda infection

Xing²,

Tang³

et al. 2022

Front. Immunol.

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The protective immune response produced by fish after vaccination is crucial for vaccine effectiveness. Our previous studies have shown inactivated vaccine against Edwardsiella tarda can induce immune response in flounder (Paralichthys olivaceus). To elucidate the protective immune response at the genetic level, in this study, flounder was immunized with inactivated E. tarda for 5 weeks, and then they were challenged with E. tarda. The spleen was dissected at 7th day post immunization, 1st and 7th day post challenge, respectively. Transcriptome analysis showed that average of 46 million clean reads were obtained per library, while percentage of clean reads being mapped to reference genome was more than 89% in all cases, which suggested good quality of samples. As for differentially expressed genes (DEGs) identification in inactivated E. tarda groups, at 7th day post immunization, 1422 DEGs were identified and significantly enriched in innate immune-related pathways, such as Phagosome, Cell adhesion molecules and NF-kappa B signaling pathway; At 1st post challenge day, 1210 DEGs were identified and enriched to Antigen processing and presentation and Cell adhesion molecules, indicating that the pathogen was rapidly recognized and delivered; At 7th post challenge day, 1929 DEGs were identified, belonged to Toll-like receptor signaling pathway, Antigen processing and presentation, Th1 and Th2 cell differentiation and Th17 cell differentiation. Compared to 7th post immunization day, 73 immune-associated DEGs were identified at 1st post challenge day. Protein-protein interaction networks analysis revealed 11 hub genes (TLR7, TLR3, CXCR4, IFIH1, TLR8 etc), associated with recognition of pathogens and activation of innate immunity; while for 7th post challenge day, 141 immune-associated DEGs were identified. 30 hub genes (IL6, STAT1, HSP90A.1, TLR7, IL12β etc) were associated with stimulation of lymphocyte differentiation and activation of cellular immunity. Ten immune-related genes were randomly selected for RT-qPCR validation at each time point. In conclusion, data revealed protection of flounder against E. tarda infection by inactivated vaccine is mediated via immediate recognition of pathogen and subsequently activation of cellular immunity. Results give new aspect for vaccine protection cascades, is good references for vaccine evaluation.

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“…Hence, effective activation of APCs is a prerequisite for TAAs to trigger the tumor-immunity cycle. For DC maturation, various methods have been brought up, such as nucleic acid-based vaccine 127 , 128 , calreticulin 129 , and toll-like receptor (TLR) agonists 130 , 131 , which all manifest great prospects. Moreover, Liu et al.…”

Section: Strategies For Remodeling Immunosuppressive Tmementioning

confidence: 99%

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Xiong

Sun

et al. 2022

Acta Pharmaceutica Sinica B

114

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Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics

Cited by 86 publications

References 146 publications

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Splenic protection network revealed by transcriptome analysis in inactivated vaccine-immunized flounder (Paralichthys olivaceus) against Edwardsiella tarda infection

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

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