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Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy

Hypoxia leads to up‐regulation of PD‐L1 and decreases T lymphocyte infiltration, thus boosting immunotherapeutic resistance of tumors. Moreover, tumor‐infiltrating myeloid cells such as myeloid‐derived suppressor cells (MDSCs) correlate with potent immune suppressive activity and resistance to the i...

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Autores principales: Yu, Meng, Duan, Xiaohui, Cai, Yujun, Zhang, Fang, Jiang, Shuqi, Han, Shisong, Shen, Jun, Shuai, Xintao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702652/
https://www.ncbi.nlm.nih.gov/pubmed/31453054
http://dx.doi.org/10.1002/advs.201900037
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author Yu, Meng
Duan, Xiaohui
Cai, Yujun
Zhang, Fang
Jiang, Shuqi
Han, Shisong
Shen, Jun
Shuai, Xintao
author_facet Yu, Meng
Duan, Xiaohui
Cai, Yujun
Zhang, Fang
Jiang, Shuqi
Han, Shisong
Shen, Jun
Shuai, Xintao
author_sort Yu, Meng
collection PubMed
description Hypoxia leads to up‐regulation of PD‐L1 and decreases T lymphocyte infiltration, thus boosting immunotherapeutic resistance of tumors. Moreover, tumor‐infiltrating myeloid cells such as myeloid‐derived suppressor cells (MDSCs) correlate with potent immune suppressive activity and resistance to the immune checkpoint blocking (ICB) in tumor sites. Here, a multifunctional nanoregulator incorporating MnO(2) particles and small molecular IPI549 is developed, which can reshape the tumor immune microenvironment (TIME) to unleash the immune system. The intravenously administered nanoregulator effectively accumulates in tumor sites to alleviate hypoxia via oxygen‐generating reduction of MnO(2) and to inhibit PI3Kγ on MDSCs via IPI549 release in the tumor microenvironment (TME), which results in concurrent downregulation of PD‐L1 expression, polarization of tumor associated macrophages (TAMs) toward pro‐inflammatory M1‐like phenotype (tumor‐suppressive), enhanced infiltration of CD4(+) helper T lymphocytes (Th cells), and cytotoxic CD8(+) T lymphocytes (Tc cells), and suppressed infiltration of regulatory T lymphocytes (T(reg) cells) for effective tumor immunotherapy. Furthermore, the local generation of Mn(2+) in TME allows tumor‐specific magnetic resonance imaging (MRI). More excitingly, the nanoregulator‐reshaped TIME is effectively reserved due to the synergistic effect of hypoxia alleviation and MDSC PI3Kγ inhibition, leading to remarkable post‐medication inhibition of tumor re‐growth and metastasis in an animal study.
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spelling pubmed-67026522019-08-26 Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy Yu, Meng Duan, Xiaohui Cai, Yujun Zhang, Fang Jiang, Shuqi Han, Shisong Shen, Jun Shuai, Xintao Adv Sci (Weinh) Full Papers Hypoxia leads to up‐regulation of PD‐L1 and decreases T lymphocyte infiltration, thus boosting immunotherapeutic resistance of tumors. Moreover, tumor‐infiltrating myeloid cells such as myeloid‐derived suppressor cells (MDSCs) correlate with potent immune suppressive activity and resistance to the immune checkpoint blocking (ICB) in tumor sites. Here, a multifunctional nanoregulator incorporating MnO(2) particles and small molecular IPI549 is developed, which can reshape the tumor immune microenvironment (TIME) to unleash the immune system. The intravenously administered nanoregulator effectively accumulates in tumor sites to alleviate hypoxia via oxygen‐generating reduction of MnO(2) and to inhibit PI3Kγ on MDSCs via IPI549 release in the tumor microenvironment (TME), which results in concurrent downregulation of PD‐L1 expression, polarization of tumor associated macrophages (TAMs) toward pro‐inflammatory M1‐like phenotype (tumor‐suppressive), enhanced infiltration of CD4(+) helper T lymphocytes (Th cells), and cytotoxic CD8(+) T lymphocytes (Tc cells), and suppressed infiltration of regulatory T lymphocytes (T(reg) cells) for effective tumor immunotherapy. Furthermore, the local generation of Mn(2+) in TME allows tumor‐specific magnetic resonance imaging (MRI). More excitingly, the nanoregulator‐reshaped TIME is effectively reserved due to the synergistic effect of hypoxia alleviation and MDSC PI3Kγ inhibition, leading to remarkable post‐medication inhibition of tumor re‐growth and metastasis in an animal study. John Wiley and Sons Inc. 2019-06-17 /pmc/articles/PMC6702652/ /pubmed/31453054 http://dx.doi.org/10.1002/advs.201900037 Text en © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Yu, Meng
Duan, Xiaohui
Cai, Yujun
Zhang, Fang
Jiang, Shuqi
Han, Shisong
Shen, Jun
Shuai, Xintao
Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
title Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
title_full Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
title_fullStr Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
title_full_unstemmed Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
title_short Multifunctional Nanoregulator Reshapes Immune Microenvironment and Enhances Immune Memory for Tumor Immunotherapy
title_sort multifunctional nanoregulator reshapes immune microenvironment and enhances immune memory for tumor immunotherapy
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702652/
https://www.ncbi.nlm.nih.gov/pubmed/31453054
http://dx.doi.org/10.1002/advs.201900037
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