Tumours with an immunosuppressive microenvironment respond poorly to therapy. Activation of the stimulator of interferon genes (STING) pathway can enhance intratumoural immune activation, but STING agonists are associated with high toxicity and degrade prematurely, which limits their effectiveness. Here, we show that the extended intratumoural release of the STING agonist cyclic di-AMP transforms the tumour microenvironment from immunosuppressive to immunostimulatory, increasing the efficacy of antitumour therapies. The STING agonist was electrostatically complexed with nanotubes comprising a peptide–drug conjugate (a peptide that binds to the protein neuropilin-1, which is highly expressed in tumours, and the chemotherapeutic agent camptothecin) that self-assemble in situ into a supramolecular hydrogel. In multiple mouse models of murine tumours, a single low dose of the STING agonist led to tumour regression and increased animal survival, and to long-term immunological memory and systemic immune surveillance, which protected the mice against tumour recurrence and the formation of metastases. Locally delivered STING agonists could help to reduce tumour immunosuppression and enhance the efficacy of a wide range of cancer therapies.

具有免疫抑制微环境的肿瘤对治疗反应不佳。干扰素基因刺激物 (STING) 通路的激活可以增强肿瘤内免疫激活，但 STING 激动剂具有高毒性和过早降解，这限制了它们的有效性。在这里，我们表明 STING 激动剂环状 di-AMP 在肿瘤内的延长释放将肿瘤微环境从免疫抑制转变为免疫刺激，从而提高了抗肿瘤治疗的疗效。STING 激动剂与纳米管静电复合，纳米管包含一种肽-药物偶联物（一种与神经毡蛋白-1 结合的肽，在肿瘤中高度表达，以及化疗药物喜树碱），纳米管原位自组装成超分子水凝胶。在小鼠肿瘤的多种小鼠模型中，单一低剂量的 STING 激动剂导致肿瘤消退并增加动物存活率，并导致长期免疫记忆和全身免疫监视，从而保护小鼠免受肿瘤复发和转移的形成。局部递送的 STING 激动剂可以帮助减少肿瘤免疫抑制并增强多种癌症疗法的疗效。