Phytochemical natural killer cells reprogram tumor microenvironment for potent immunotherapy of solid tumors

Yao Lei; Helin Zhao; Yuzhu Wu; Lili Huang; Weidong Nie; Houli Liu; Guanghao Wu; Dai-Wen Pang; Hai-Yan Xie

doi:10.1016/j.biomaterials.2022.121635

Phytochemical natural killer cells reprogram tumor microenvironment for potent immunotherapy of solid tumors

Biomaterials. 2022 Aug:287:121635. doi: 10.1016/j.biomaterials.2022.121635. Epub 2022 Jun 15.

Authors

Yao Lei¹, Helin Zhao¹, Yuzhu Wu¹, Lili Huang¹, Weidong Nie¹, Houli Liu¹, Guanghao Wu¹, Dai-Wen Pang², Hai-Yan Xie³

Affiliations

¹ School of Life Science, Beijing Institute of Technology, Beijing, 100081, PR China.
² College of Chemistry, Nankai University, Tianjin, 300071, PR China.
³ School of Life Science, Beijing Institute of Technology, Beijing, 100081, PR China. Electronic address: hyanxie@bit.edu.cn.

PMID: 35921728
DOI: 10.1016/j.biomaterials.2022.121635

Abstract

Natural killer cells (NKs) hold great promise in cancer treatment, but their application in solid tumors remains a great challenge because current solutions hardly can overcome various difficulties that faced. Herein, we endow NKs with the phytochemical feature for effective immunotherapy of solid tumors. NKs are decorated with natural thylakoid (Tk) membranes through an efficient and convenient membrane fusion strategy. Tk engineering effectively activates NKs, because the antioxidase on Tk induce glycogen synthase kinase-3β inhibition, and subsequently increase the expression of activating receptor and cytotoxic effector molecules in NKs. After systemic administration, the phytochemical NKs (PC-NKs) can target tumor tissues, and then profoundly reprogram tumor microenvironment (TME) with the help of catalase on Tk, resulting in significantly enhanced direct killing of PC-NKs and immune activated TME. Therefore, potent therapeutic effects with few abnormalities are achieved, providing a novel idea for the development of highly efficient NKs for solid tumors.

Keywords: Natural killer cell; Phytochemical; Solid tumor; Thylakoid.