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

Wenquan Ou, Samantha Stewart, Alisa White, Elyahb A. Kwizera, Jiangsheng Xu, Yuanzhang Fang, James G. Shamul, Changqing Xie, Suliat Nurudeen, Nikki P. Tirada, Xiongbin Lu, Katherine H. R. Tkaczuk and Xiaoming He ()
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Wenquan Ou: University of Maryland
Samantha Stewart: University of Maryland
Alisa White: University of Maryland
Elyahb A. Kwizera: University of Maryland
Jiangsheng Xu: University of Maryland
Yuanzhang Fang: Indiana University School of Medicine
James G. Shamul: University of Maryland
Changqing Xie: National Institutes of Health
Suliat Nurudeen: University of Maryland
Nikki P. Tirada: University of Maryland
Xiongbin Lu: Indiana University School of Medicine
Katherine H. R. Tkaczuk: University of Maryland
Xiaoming He: University of Maryland

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36045-7

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