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Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors

The failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dual-mechanism based CTLs infil...

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Autores principales: Huang, Yukun, Chen, Yu, Zhou, Songlei, Chen, Liang, Wang, Jiahao, Pei, Yuanyuan, Xu, Minjun, Feng, Jingxian, Jiang, Tianze, Liang, Kaifan, Liu, Shanshan, Song, Qingxiang, Jiang, Gan, Gu, Xiao, Zhang, Qian, Gao, Xiaoling, Chen, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992734/
https://www.ncbi.nlm.nih.gov/pubmed/32001695
http://dx.doi.org/10.1038/s41467-020-14425-7
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author Huang, Yukun
Chen, Yu
Zhou, Songlei
Chen, Liang
Wang, Jiahao
Pei, Yuanyuan
Xu, Minjun
Feng, Jingxian
Jiang, Tianze
Liang, Kaifan
Liu, Shanshan
Song, Qingxiang
Jiang, Gan
Gu, Xiao
Zhang, Qian
Gao, Xiaoling
Chen, Jun
author_facet Huang, Yukun
Chen, Yu
Zhou, Songlei
Chen, Liang
Wang, Jiahao
Pei, Yuanyuan
Xu, Minjun
Feng, Jingxian
Jiang, Tianze
Liang, Kaifan
Liu, Shanshan
Song, Qingxiang
Jiang, Gan
Gu, Xiao
Zhang, Qian
Gao, Xiaoling
Chen, Jun
author_sort Huang, Yukun
collection PubMed
description The failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dual-mechanism based CTLs infiltration enhancer, Nano-sapper, which can simultaneously reduce the physical obstacles in tumor microenvironment and recruiting CTLs to potentiate immunotherapy in IET. Nano-sapper consists a core that co-loaded with antifibrotic phosphates-modified α-mangostin and plasmid encoding immune-enhanced cytokine LIGHT. Through reversing the abnormal activated fibroblasts, decreasing collagen deposition, normalizing the intratumoral vasculatures, and in situ stimulating the lymphocyte-recruiting chemoattractants expression, Nano-sapper paves the road for the CTLs infiltration, induces the intratumoral tertiary lymphoid structures, thus reshapes tumor microenvironment and potentiates checkpoint inhibitor against IET. This study demonstrates that the combination of antifibrotic agent and immune-enhanced cytokine might represent a modality in promoting immunotherapy against IET.
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spelling pubmed-69927342020-02-03 Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors Huang, Yukun Chen, Yu Zhou, Songlei Chen, Liang Wang, Jiahao Pei, Yuanyuan Xu, Minjun Feng, Jingxian Jiang, Tianze Liang, Kaifan Liu, Shanshan Song, Qingxiang Jiang, Gan Gu, Xiao Zhang, Qian Gao, Xiaoling Chen, Jun Nat Commun Article The failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dual-mechanism based CTLs infiltration enhancer, Nano-sapper, which can simultaneously reduce the physical obstacles in tumor microenvironment and recruiting CTLs to potentiate immunotherapy in IET. Nano-sapper consists a core that co-loaded with antifibrotic phosphates-modified α-mangostin and plasmid encoding immune-enhanced cytokine LIGHT. Through reversing the abnormal activated fibroblasts, decreasing collagen deposition, normalizing the intratumoral vasculatures, and in situ stimulating the lymphocyte-recruiting chemoattractants expression, Nano-sapper paves the road for the CTLs infiltration, induces the intratumoral tertiary lymphoid structures, thus reshapes tumor microenvironment and potentiates checkpoint inhibitor against IET. This study demonstrates that the combination of antifibrotic agent and immune-enhanced cytokine might represent a modality in promoting immunotherapy against IET. Nature Publishing Group UK 2020-01-30 /pmc/articles/PMC6992734/ /pubmed/32001695 http://dx.doi.org/10.1038/s41467-020-14425-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Huang, Yukun
Chen, Yu
Zhou, Songlei
Chen, Liang
Wang, Jiahao
Pei, Yuanyuan
Xu, Minjun
Feng, Jingxian
Jiang, Tianze
Liang, Kaifan
Liu, Shanshan
Song, Qingxiang
Jiang, Gan
Gu, Xiao
Zhang, Qian
Gao, Xiaoling
Chen, Jun
Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
title Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
title_full Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
title_fullStr Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
title_full_unstemmed Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
title_short Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
title_sort dual-mechanism based ctls infiltration enhancement initiated by nano-sapper potentiates immunotherapy against immune-excluded tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992734/
https://www.ncbi.nlm.nih.gov/pubmed/32001695
http://dx.doi.org/10.1038/s41467-020-14425-7
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