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

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dc.contributor.authorOu, Wenquan
dc.contributor.authorStewart, Samantha
dc.contributor.authorWhite, Alisa
dc.contributor.authorKwizera, Elyahb A.
dc.contributor.authorXu, Jiangsheng
dc.contributor.authorFang, Yuanzheng
dc.contributor.authorShamul, James G.
dc.contributor.authorXie, Changqing
dc.contributor.authorNurudeen, Suliat
dc.contributor.authorTirada, Nikki P.
dc.contributor.authorLu, Xiongbin
dc.contributor.authorTkaczuk, Katherine H.R.
dc.contributor.authorHe, Xiaoming
dc.date.accessioned2023-09-11T17:23:34Z
dc.date.available2023-09-11T17:23:34Z
dc.date.issued2023-01-24
dc.descriptionPartial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.
dc.description.abstractCancer 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.
dc.description.urihttps://doi.org/10.1038/s41467-023-36045-7
dc.identifierhttps://doi.org/10.13016/dspace/qqlj-db4j
dc.identifier.citationOu, W., Stewart, S., White, A. et al. In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy. Nat Commun 14, 392 (2023).
dc.identifier.urihttp://hdl.handle.net/1903/30453
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isAvailableAtA. James Clark School of Engineeringen_us
dc.relation.isAvailableAtFischell Department of Bioengineeringen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.titleIn-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
dc.typeArticle
local.equitableAccessSubmissionNo

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