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Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives

Toll-like receptors (TLRs) serve as the body’s first line of defense, recognizing both pathogen-expressed molecules and host-derived molecules released from damaged or dying cells. The wide distribution of different cell types, ranging from epithelial to immune cells, highlights the crucial roles of...

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Autores principales: Mukherjee, Suprabhat, Patra, Ritwik, Behzadi, Payam, Masotti, Andrea, Paolini, Alessandro, Sarshar, Meysam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562563/
https://www.ncbi.nlm.nih.gov/pubmed/37822929
http://dx.doi.org/10.3389/fimmu.2023.1244345
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author Mukherjee, Suprabhat
Patra, Ritwik
Behzadi, Payam
Masotti, Andrea
Paolini, Alessandro
Sarshar, Meysam
author_facet Mukherjee, Suprabhat
Patra, Ritwik
Behzadi, Payam
Masotti, Andrea
Paolini, Alessandro
Sarshar, Meysam
author_sort Mukherjee, Suprabhat
collection PubMed
description Toll-like receptors (TLRs) serve as the body’s first line of defense, recognizing both pathogen-expressed molecules and host-derived molecules released from damaged or dying cells. The wide distribution of different cell types, ranging from epithelial to immune cells, highlights the crucial roles of TLRs in linking innate and adaptive immunity. Upon stimulation, TLRs binding mediates the expression of several adapter proteins and downstream kinases, that lead to the induction of several other signaling molecules such as key pro-inflammatory mediators. Indeed, extraordinary progress in immunobiological research has suggested that TLRs could represent promising targets for the therapeutic intervention of inflammation-associated diseases, autoimmune diseases, microbial infections as well as human cancers. So far, for the prevention and possible treatment of inflammatory diseases, various TLR antagonists/inhibitors have shown to be efficacious at several stages from pre-clinical evaluation to clinical trials. Therefore, the fascinating role of TLRs in modulating the human immune responses at innate as well as adaptive levels directed the scientists to opt for these immune sensor proteins as suitable targets for developing chemotherapeutics and immunotherapeutics against cancer. Hitherto, several TLR-targeting small molecules (e.g., Pam3CSK4, Poly (I:C), Poly (A:U)), chemical compounds, phytocompounds (e.g., Curcumin), peptides, and antibodies have been found to confer protection against several types of cancers. However, administration of inappropriate doses of such TLR-modulating therapeutics or a wrong infusion administration is reported to induce detrimental outcomes. This review summarizes the current findings on the molecular and structural biology of TLRs and gives an overview of the potency and promises of TLR-directed therapeutic strategies against cancers by discussing the findings from established and pipeline discoveries.
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spelling pubmed-105625632023-10-11 Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives Mukherjee, Suprabhat Patra, Ritwik Behzadi, Payam Masotti, Andrea Paolini, Alessandro Sarshar, Meysam Front Immunol Immunology Toll-like receptors (TLRs) serve as the body’s first line of defense, recognizing both pathogen-expressed molecules and host-derived molecules released from damaged or dying cells. The wide distribution of different cell types, ranging from epithelial to immune cells, highlights the crucial roles of TLRs in linking innate and adaptive immunity. Upon stimulation, TLRs binding mediates the expression of several adapter proteins and downstream kinases, that lead to the induction of several other signaling molecules such as key pro-inflammatory mediators. Indeed, extraordinary progress in immunobiological research has suggested that TLRs could represent promising targets for the therapeutic intervention of inflammation-associated diseases, autoimmune diseases, microbial infections as well as human cancers. So far, for the prevention and possible treatment of inflammatory diseases, various TLR antagonists/inhibitors have shown to be efficacious at several stages from pre-clinical evaluation to clinical trials. Therefore, the fascinating role of TLRs in modulating the human immune responses at innate as well as adaptive levels directed the scientists to opt for these immune sensor proteins as suitable targets for developing chemotherapeutics and immunotherapeutics against cancer. Hitherto, several TLR-targeting small molecules (e.g., Pam3CSK4, Poly (I:C), Poly (A:U)), chemical compounds, phytocompounds (e.g., Curcumin), peptides, and antibodies have been found to confer protection against several types of cancers. However, administration of inappropriate doses of such TLR-modulating therapeutics or a wrong infusion administration is reported to induce detrimental outcomes. This review summarizes the current findings on the molecular and structural biology of TLRs and gives an overview of the potency and promises of TLR-directed therapeutic strategies against cancers by discussing the findings from established and pipeline discoveries. Frontiers Media S.A. 2023-09-26 /pmc/articles/PMC10562563/ /pubmed/37822929 http://dx.doi.org/10.3389/fimmu.2023.1244345 Text en Copyright © 2023 Mukherjee, Patra, Behzadi, Masotti, Paolini and Sarshar https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Mukherjee, Suprabhat
Patra, Ritwik
Behzadi, Payam
Masotti, Andrea
Paolini, Alessandro
Sarshar, Meysam
Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
title Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
title_full Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
title_fullStr Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
title_full_unstemmed Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
title_short Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
title_sort toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562563/
https://www.ncbi.nlm.nih.gov/pubmed/37822929
http://dx.doi.org/10.3389/fimmu.2023.1244345
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