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In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy

Cancer immunotherapy that deploys the host’s immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-imm...

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Autores principales: Ou, Wenquan, Stewart, Samantha, White, Alisa, Kwizera, Elyahb A., Xu, Jiangsheng, Fang, Yuanzhang, Shamul, James G., Xie, Changqing, Nurudeen, Suliat, Tirada, Nikki P., Lu, Xiongbin, Tkaczuk, Katherine H. R., He, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873931/
https://www.ncbi.nlm.nih.gov/pubmed/36693842
http://dx.doi.org/10.1038/s41467-023-36045-7
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author Ou, Wenquan
Stewart, Samantha
White, Alisa
Kwizera, Elyahb A.
Xu, Jiangsheng
Fang, Yuanzhang
Shamul, James G.
Xie, Changqing
Nurudeen, Suliat
Tirada, Nikki P.
Lu, Xiongbin
Tkaczuk, Katherine H. R.
He, Xiaoming
author_facet Ou, Wenquan
Stewart, Samantha
White, Alisa
Kwizera, Elyahb A.
Xu, Jiangsheng
Fang, Yuanzhang
Shamul, James G.
Xie, Changqing
Nurudeen, Suliat
Tirada, Nikki P.
Lu, Xiongbin
Tkaczuk, Katherine H. R.
He, Xiaoming
author_sort Ou, Wenquan
collection PubMed
description Cancer immunotherapy that deploys the host’s immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-immune engineering (ICIE) strategy for turning the TME from immunologically “cold” into “hot”. In particular, after the ICIE treatment, the ratio of the CD8(+) cytotoxic T cells to the immunosuppressive regulatory T cells is increased by more than 100 times in not only the primary tumors with cryosurgery but also distant tumors without freezing. This is achieved by combining cryosurgery that causes “frostbite” of tumor with cold-responsive nanoparticles that not only target tumor but also rapidly release both anticancer drug and PD-L1 silencing siRNA specifically into the cytosol upon cryosurgery. This ICIE treatment leads to potent immunogenic cell death, which promotes maturation of dendritic cells and activation of CD8(+) cytotoxic T cells as well as memory T cells to kill not only primary but also distant/metastatic breast tumors in female mice (i.e., the abscopal effect). Collectively, ICIE may enable an efficient and durable way to leverage the immune system for combating cancer and its metastasis.
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spelling pubmed-98739312023-01-26 In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy Ou, Wenquan Stewart, Samantha White, Alisa Kwizera, Elyahb A. Xu, Jiangsheng Fang, Yuanzhang Shamul, James G. Xie, Changqing Nurudeen, Suliat Tirada, Nikki P. Lu, Xiongbin Tkaczuk, Katherine H. R. He, Xiaoming Nat Commun Article Cancer immunotherapy that deploys the host’s immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-immune engineering (ICIE) strategy for turning the TME from immunologically “cold” into “hot”. In particular, after the ICIE treatment, the ratio of the CD8(+) cytotoxic T cells to the immunosuppressive regulatory T cells is increased by more than 100 times in not only the primary tumors with cryosurgery but also distant tumors without freezing. This is achieved by combining cryosurgery that causes “frostbite” of tumor with cold-responsive nanoparticles that not only target tumor but also rapidly release both anticancer drug and PD-L1 silencing siRNA specifically into the cytosol upon cryosurgery. This ICIE treatment leads to potent immunogenic cell death, which promotes maturation of dendritic cells and activation of CD8(+) cytotoxic T cells as well as memory T cells to kill not only primary but also distant/metastatic breast tumors in female mice (i.e., the abscopal effect). Collectively, ICIE may enable an efficient and durable way to leverage the immune system for combating cancer and its metastasis. Nature Publishing Group UK 2023-01-24 /pmc/articles/PMC9873931/ /pubmed/36693842 http://dx.doi.org/10.1038/s41467-023-36045-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ou, Wenquan
Stewart, Samantha
White, Alisa
Kwizera, Elyahb A.
Xu, Jiangsheng
Fang, Yuanzhang
Shamul, James G.
Xie, Changqing
Nurudeen, Suliat
Tirada, Nikki P.
Lu, Xiongbin
Tkaczuk, Katherine H. R.
He, Xiaoming
In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
title In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
title_full In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
title_fullStr In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
title_full_unstemmed In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
title_short In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
title_sort in-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873931/
https://www.ncbi.nlm.nih.gov/pubmed/36693842
http://dx.doi.org/10.1038/s41467-023-36045-7
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