Chimeric antigen receptor (CAR) T cell-based immunotherapy, approved by the US Food and Drug Administration, has shown curative potential in patients with haematological malignancies. However, owing to the lack of control over the location and duration of the anti-tumour immune response, CAR T cell therapy still faces safety challenges arising from cytokine release syndrome and on-target, off-tumour toxicity. Herein, we present the design of light-switchable CAR (designated LiCAR) T cells that allow real-time phototunable activation of therapeutic T cells to precisely induce tumour cell killing. When coupled with imaging-guided, surgically removable upconversion nanoplates that have enhanced near-infrared-to-blue upconversion luminescence as miniature deep-tissue photon transducers, LiCAR T cells enable both spatial and temporal control over T cell-mediated anti-tumour therapeutic activity in vivo with greatly mitigated side effects. Our nano-optogenetic immunomodulation platform not only provides a unique approach to interrogate CAR-mediated anti-tumour immunity, but also sets the stage for developing precision medicine to deliver personalized anticancer therapy.

美国食品和药物管理局批准的基于嵌合抗原受体（CAR）T 细胞的免疫疗法已显示出对血液恶性肿瘤患者的治疗潜力。然而，由于缺乏对抗肿瘤免疫反应的部位和持续时间的控制，CAR T细胞治疗仍然面临着细胞因子释放综合征和靶向、脱瘤毒性带来的安全挑战。在此，我们提出了光控 CAR（指定为 LiCAR）T 细胞的设计，它允许实时光可调激活治疗性 T 细胞，从而精确诱导肿瘤细胞杀伤。当与成像引导、可通过手术移除的上转换纳米板（作为微型深层组织光子传感器）增强近红外到蓝色上转换发光时，LiCAR T 细胞能够在空间和时间上控制 T 细胞介导的抗肿瘤治疗活性体内副作用大大减轻。我们的纳米光遗传学免疫调节平台不仅提供了一种独特的方法来研究 CAR 介导的抗肿瘤免疫，而且还为开发精准医学以提供个性化抗癌治疗奠定了基础。