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Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity

Immune‐enhancing adjuvants usually targets antigen (Ag)‐presenting cells to tune up cellular and humoral immunity. CD141(+) dendritic cells (DC) represent the professional Ag‐presenting cells in humans. In response to microbial pattern molecules, these DCs upgrade the maturation stage sufficient to...

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Autores principales: Seya, Tsukasa, Shime, Hiroaki, Takeda, Yohei, Tatematsu, Megumi, Takashima, Ken, Matsumoto, Misako
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714660/
https://www.ncbi.nlm.nih.gov/pubmed/26395101
http://dx.doi.org/10.1111/cas.12824
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author Seya, Tsukasa
Shime, Hiroaki
Takeda, Yohei
Tatematsu, Megumi
Takashima, Ken
Matsumoto, Misako
author_facet Seya, Tsukasa
Shime, Hiroaki
Takeda, Yohei
Tatematsu, Megumi
Takashima, Ken
Matsumoto, Misako
author_sort Seya, Tsukasa
collection PubMed
description Immune‐enhancing adjuvants usually targets antigen (Ag)‐presenting cells to tune up cellular and humoral immunity. CD141(+) dendritic cells (DC) represent the professional Ag‐presenting cells in humans. In response to microbial pattern molecules, these DCs upgrade the maturation stage sufficient to improve cross‐presentation of exogenous Ag, and upregulation of MHC and costimulators, allowing CD4/CD8 T cells to proliferate and liberating cytokines/chemokines that support lymphocyte attraction and survival. These DCs also facilitate natural killer‐mediated cell damage. Toll‐like receptors (TLRs) and their signaling pathways in DCs play a pivotal role in DC maturation. Therefore, providing adjuvants in addition to Ag is indispensable for successful vaccine immunotherapy for cancer, which has been approved in comparison with antimicrobial vaccines. Mouse CD8α(+) DCs express TLR7 and TLR9 in addition to the TLR2 family (TLR1, 2, and 6) and TLR3, whereas human CD141(+) DCs exclusively express the TLR2 family and TLR3. Although human and mouse plasmacytoid DCs commonly express TLR7/9 to respond to their agonists, the results on mouse adjuvant studies using TLR7/9 agonists cannot be simply extrapolated to human adjuvant immunotherapy. In contrast, TLR2 and TLR3 are similarly expressed in both human and mouse Ag‐presenting DCs. Bacillus Calmette–Guerin peptidoglycan and polyinosinic–polycytidylic acid are representative agonists for TLR2 and TLR3, respectively, although they additionally stimulate cytoplasmic sensors: their functional specificities may not be limited to the relevant TLRs. These adjuvants have been posted up to a certain achievement in immunotherapy in some cancers. We herein summarize the history and perspectives of TLR2 and TLR3 agonists in vaccine‐adjuvant immunotherapy for cancer.
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spelling pubmed-47146602016-01-22 Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity Seya, Tsukasa Shime, Hiroaki Takeda, Yohei Tatematsu, Megumi Takashima, Ken Matsumoto, Misako Cancer Sci Review Articles Immune‐enhancing adjuvants usually targets antigen (Ag)‐presenting cells to tune up cellular and humoral immunity. CD141(+) dendritic cells (DC) represent the professional Ag‐presenting cells in humans. In response to microbial pattern molecules, these DCs upgrade the maturation stage sufficient to improve cross‐presentation of exogenous Ag, and upregulation of MHC and costimulators, allowing CD4/CD8 T cells to proliferate and liberating cytokines/chemokines that support lymphocyte attraction and survival. These DCs also facilitate natural killer‐mediated cell damage. Toll‐like receptors (TLRs) and their signaling pathways in DCs play a pivotal role in DC maturation. Therefore, providing adjuvants in addition to Ag is indispensable for successful vaccine immunotherapy for cancer, which has been approved in comparison with antimicrobial vaccines. Mouse CD8α(+) DCs express TLR7 and TLR9 in addition to the TLR2 family (TLR1, 2, and 6) and TLR3, whereas human CD141(+) DCs exclusively express the TLR2 family and TLR3. Although human and mouse plasmacytoid DCs commonly express TLR7/9 to respond to their agonists, the results on mouse adjuvant studies using TLR7/9 agonists cannot be simply extrapolated to human adjuvant immunotherapy. In contrast, TLR2 and TLR3 are similarly expressed in both human and mouse Ag‐presenting DCs. Bacillus Calmette–Guerin peptidoglycan and polyinosinic–polycytidylic acid are representative agonists for TLR2 and TLR3, respectively, although they additionally stimulate cytoplasmic sensors: their functional specificities may not be limited to the relevant TLRs. These adjuvants have been posted up to a certain achievement in immunotherapy in some cancers. We herein summarize the history and perspectives of TLR2 and TLR3 agonists in vaccine‐adjuvant immunotherapy for cancer. John Wiley and Sons Inc. 2015-11-18 2015-12 /pmc/articles/PMC4714660/ /pubmed/26395101 http://dx.doi.org/10.1111/cas.12824 Text en © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Review Articles
Seya, Tsukasa
Shime, Hiroaki
Takeda, Yohei
Tatematsu, Megumi
Takashima, Ken
Matsumoto, Misako
Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
title Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
title_full Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
title_fullStr Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
title_full_unstemmed Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
title_short Adjuvant for vaccine immunotherapy of cancer – focusing on Toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
title_sort adjuvant for vaccine immunotherapy of cancer – focusing on toll‐like receptor 2 and 3 agonists for safely enhancing antitumor immunity
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714660/
https://www.ncbi.nlm.nih.gov/pubmed/26395101
http://dx.doi.org/10.1111/cas.12824
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