Engineered algae microrobots as photosynthetic living materials promote T cells’ anti-tumor immunity

摘要

Dendritic cells (DCs) can form a T cell niche in tumor microenvironment and drive T cell proliferation through immunostimulatory ligands. However, hypoxia severely hinders the infiltration and proliferation of immune cells, thus restricting T cells’ anti-tumor response. Microalgae have evolved an efficient photosynthesis system that might be a promising oxygen source to mitigate hypoxia. Here, we combine Chlorella vulgaris and a genetically engineered DC membrane, overexpressing immunostimulatory tumor necrosis factor (TNF) ligand proteins OX40L, 4-1BBL, and CD70, to assemble a “photosynthetic micron robot,” which generates oxygen in situ to alleviate the state of hypoxia in the tumor microenvironment, thereby improving the efficiency of immunotherapy. TNF ligand proteins displayed on cell membrane nanovesicles and the photosynthetic micron robot bind to their cognate receptors on T cells and enhance the activity and proliferation of the effector T cells and memory T cells. Combined with programmed death-1 antibody, the photosynthetic micron robot prevents tumor relapse and metastasis in a mouse model.