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Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota
Toll-like receptor 2 (TLR2) expressed on myeloid cells mediates the recognition of harmful molecules belonging to invading pathogens or host damaged tissues, leading to inflammation. For this ability to activate immune responses, TLR2 has been considered a player in anti-cancer immunity. Therefore,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763461/ https://www.ncbi.nlm.nih.gov/pubmed/33321934 http://dx.doi.org/10.3390/ijms21249418 |
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author | Di Lorenzo, Antonino Bolli, Elisabetta Tarone, Lidia Cavallo, Federica Conti, Laura |
author_facet | Di Lorenzo, Antonino Bolli, Elisabetta Tarone, Lidia Cavallo, Federica Conti, Laura |
author_sort | Di Lorenzo, Antonino |
collection | PubMed |
description | Toll-like receptor 2 (TLR2) expressed on myeloid cells mediates the recognition of harmful molecules belonging to invading pathogens or host damaged tissues, leading to inflammation. For this ability to activate immune responses, TLR2 has been considered a player in anti-cancer immunity. Therefore, TLR2 agonists have been used as adjuvants for anti-cancer immunotherapies. However, TLR2 is also expressed on neoplastic cells from different malignancies and promotes their proliferation through activation of the myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway. Furthermore, its activation on regulatory immune cells may contribute to the generation of an immunosuppressive microenvironment and of the pre-metastatic niche, promoting cancer progression. Thus, TLR2 represents a double-edge sword, whose role in cancer needs to be carefully understood for the setup of effective therapies. In this review, we discuss the divergent effects induced by TLR2 activation in different immune cell populations, cancer cells, and cancer stem cells. Moreover, we analyze the stimuli that lead to its activation in the tumor microenvironment, addressing the role of danger, pathogen, and microbiota-associated molecular patterns and their modulation during cancer treatments. This information will contribute to the scientific debate on the use of TLR2 agonists or antagonists in cancer treatment and pave the way for new therapeutic avenues. |
format | Online Article Text |
id | pubmed-7763461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77634612020-12-27 Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota Di Lorenzo, Antonino Bolli, Elisabetta Tarone, Lidia Cavallo, Federica Conti, Laura Int J Mol Sci Review Toll-like receptor 2 (TLR2) expressed on myeloid cells mediates the recognition of harmful molecules belonging to invading pathogens or host damaged tissues, leading to inflammation. For this ability to activate immune responses, TLR2 has been considered a player in anti-cancer immunity. Therefore, TLR2 agonists have been used as adjuvants for anti-cancer immunotherapies. However, TLR2 is also expressed on neoplastic cells from different malignancies and promotes their proliferation through activation of the myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway. Furthermore, its activation on regulatory immune cells may contribute to the generation of an immunosuppressive microenvironment and of the pre-metastatic niche, promoting cancer progression. Thus, TLR2 represents a double-edge sword, whose role in cancer needs to be carefully understood for the setup of effective therapies. In this review, we discuss the divergent effects induced by TLR2 activation in different immune cell populations, cancer cells, and cancer stem cells. Moreover, we analyze the stimuli that lead to its activation in the tumor microenvironment, addressing the role of danger, pathogen, and microbiota-associated molecular patterns and their modulation during cancer treatments. This information will contribute to the scientific debate on the use of TLR2 agonists or antagonists in cancer treatment and pave the way for new therapeutic avenues. MDPI 2020-12-10 /pmc/articles/PMC7763461/ /pubmed/33321934 http://dx.doi.org/10.3390/ijms21249418 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Di Lorenzo, Antonino Bolli, Elisabetta Tarone, Lidia Cavallo, Federica Conti, Laura Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota |
title | Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota |
title_full | Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota |
title_fullStr | Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota |
title_full_unstemmed | Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota |
title_short | Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota |
title_sort | toll-like receptor 2 at the crossroad between cancer cells, the immune system, and the microbiota |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763461/ https://www.ncbi.nlm.nih.gov/pubmed/33321934 http://dx.doi.org/10.3390/ijms21249418 |
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