Abstract
Lytic cell death triggers an antitumour immune response. However, cancer cells evade lytic cell death by several mechanisms. Moreover, a prolonged and uncontrolled immune response conversely leads to T-cell exhaustion. Therefore, an oncolytic system capable of eliciting an immune response by killing cancer cells in a controlled manner is needed. Here, we establish a micro-scale cytotoxic T-cell-inspired oncolytic system (TIOs) to precisely lyse cancer cells by NIR-light-controlled lipid peroxidation. Our TIOs present antigen-based cell recognition, tumour-targeting and catalytic cell-lysis ability; thus, the TIOs induce oncolysis in vivo. We apply TIOs to preclinical cancer models, showing anti-tumor activity with negligible side-effects. Tumour regression is correlated with a T-cell based anti-tumour immune response and TIOs also improve responses to anti-PD-1 therapy or STING activation. Our study provides insights to design oncolytic systems for antitumour immunity. Moreover, activation of STING can reverse T-cell exhaustion in oncolysis.