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.

裂解细胞死亡会触发抗肿瘤免疫反应。然而，癌细胞通过多种机制逃避裂解细胞死亡。此外，长期且不受控制的免疫反应反而会导致 T 细胞耗竭。因此，需要一种能够通过以受控方式杀死癌细胞来引发免疫反应的溶瘤系统。在这里，我们建立了一种微型细胞毒性 T 细胞启发的溶瘤系统 (TIO)，通过近红外光控制的脂质过氧化作用精确裂解癌细胞。我们的 TIO 具有基于抗原的细胞识别、肿瘤靶向和催化细胞裂解能力；因此，TIO 在体内诱导溶瘤作用。我们将 TIO 应用于临床前癌症模型，显示出抗肿瘤活性且副作用可忽略不计。肿瘤消退与基于 T 细胞的抗肿瘤免疫反应相关，TIO 还可以改善对抗 PD-1 治疗或 STING 激活的反应。我们的研究为设计抗肿瘤免疫溶瘤系统提供了见解。此外，STING 的激活可以逆转溶瘤过程中 T 细胞的耗竭。