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Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension

The deficiency of antigen‐specific T cells and the induction of various treatment‐induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo‐immunotherapy adjuvanted with Toll‐like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and...

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Autores principales: Jin, Seung Mo, Lee, Sang Nam, Kim, Jung Eun, Yoo, Yeon Jeong, Song, Chanyoung, Shin, Hong Sik, Phuengkham, Hathaichanok, Lee, Chang Hoon, Um, Soong Ho, Lim, Yong Taik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498862/
https://www.ncbi.nlm.nih.gov/pubmed/34363349
http://dx.doi.org/10.1002/advs.202102043
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author Jin, Seung Mo
Lee, Sang Nam
Kim, Jung Eun
Yoo, Yeon Jeong
Song, Chanyoung
Shin, Hong Sik
Phuengkham, Hathaichanok
Lee, Chang Hoon
Um, Soong Ho
Lim, Yong Taik
author_facet Jin, Seung Mo
Lee, Sang Nam
Kim, Jung Eun
Yoo, Yeon Jeong
Song, Chanyoung
Shin, Hong Sik
Phuengkham, Hathaichanok
Lee, Chang Hoon
Um, Soong Ho
Lim, Yong Taik
author_sort Jin, Seung Mo
collection PubMed
description The deficiency of antigen‐specific T cells and the induction of various treatment‐induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo‐immunotherapy adjuvanted with Toll‐like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and in situ vaccination effect, indoleamine 2,3‐dioxygenase (IDO) is also significantly increased in the tumor microenvironment (TME) and tumor‐draining lymph node (TDLN), which offsets the activated antitumor immunity. To address the treatment‐induced immunosuppression, an assemblable immune modulating suspension (AIMS) containing ICD inducer (paclitaxel) and supra‐adjuvant (immune booster; R848 as a TLR 7/8a, immunosuppression reliever; epacadostat as an IDO inhibitor) is suggested and shows that it increases cytotoxic T lymphocytes and relieves the IDO‐related immunosuppression (TGF‐β, IL‐10, myeloid‐derived suppressor cells, and regulatory T cells) in both TME and TDLN, by the formation of in situ depot in tumor bed as well as by the efficient migration into TDLN. Local administration of AIMS increases T cell infiltration in both local and distant tumors and significantly inhibits the metastasis of tumors to the lung. Reverting treatment‐induced secondary immunosuppression and reshaping “cold tumor” into “hot tumor” by AIMS also increases the response rate of immune checkpoint blockade therapy, which promises a new nanotheranostic strategy in cancer immunotherapy.
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spelling pubmed-84988622021-10-12 Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension Jin, Seung Mo Lee, Sang Nam Kim, Jung Eun Yoo, Yeon Jeong Song, Chanyoung Shin, Hong Sik Phuengkham, Hathaichanok Lee, Chang Hoon Um, Soong Ho Lim, Yong Taik Adv Sci (Weinh) Research Articles The deficiency of antigen‐specific T cells and the induction of various treatment‐induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo‐immunotherapy adjuvanted with Toll‐like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and in situ vaccination effect, indoleamine 2,3‐dioxygenase (IDO) is also significantly increased in the tumor microenvironment (TME) and tumor‐draining lymph node (TDLN), which offsets the activated antitumor immunity. To address the treatment‐induced immunosuppression, an assemblable immune modulating suspension (AIMS) containing ICD inducer (paclitaxel) and supra‐adjuvant (immune booster; R848 as a TLR 7/8a, immunosuppression reliever; epacadostat as an IDO inhibitor) is suggested and shows that it increases cytotoxic T lymphocytes and relieves the IDO‐related immunosuppression (TGF‐β, IL‐10, myeloid‐derived suppressor cells, and regulatory T cells) in both TME and TDLN, by the formation of in situ depot in tumor bed as well as by the efficient migration into TDLN. Local administration of AIMS increases T cell infiltration in both local and distant tumors and significantly inhibits the metastasis of tumors to the lung. Reverting treatment‐induced secondary immunosuppression and reshaping “cold tumor” into “hot tumor” by AIMS also increases the response rate of immune checkpoint blockade therapy, which promises a new nanotheranostic strategy in cancer immunotherapy. John Wiley and Sons Inc. 2021-08-07 /pmc/articles/PMC8498862/ /pubmed/34363349 http://dx.doi.org/10.1002/advs.202102043 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Jin, Seung Mo
Lee, Sang Nam
Kim, Jung Eun
Yoo, Yeon Jeong
Song, Chanyoung
Shin, Hong Sik
Phuengkham, Hathaichanok
Lee, Chang Hoon
Um, Soong Ho
Lim, Yong Taik
Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension
title Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension
title_full Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension
title_fullStr Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension
title_full_unstemmed Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension
title_short Overcoming Chemoimmunotherapy‐Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension
title_sort overcoming chemoimmunotherapy‐induced immunosuppression by assemblable and depot forming immune modulating nanosuspension
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498862/
https://www.ncbi.nlm.nih.gov/pubmed/34363349
http://dx.doi.org/10.1002/advs.202102043
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