Immune checkpoint blockade therapy is revolutionizing the traditional treatment model of multiple tumor types, but remains ineffective for a large subset of patients. Photodynamic therapy (PDT) has been shown to induce cancer cell death and provoke an immune response, and may represent a potential strategy to synergize with immune checkpoint blockade therapy. However, the limited tissue penetration of exciting light for conventional PDT largely hinders its application in the clinic and its further combination with immunotherapy. Here, a serrated packing covalent organic framework (COF), COF-606, with excellent two-photon absorption (2PA) property and photostability, largely avoids aggregation-caused quenching, therefore offering high reactive oxygen species (ROS) generation efficiency; it is used as a 2PA photosensitizer for PDT in deep tumor tissue. COF-606 induced PDT is shown to be efficient in inducing immunogenic cell death, provoking an immune response and normalizing the immunosuppressive status for the first time. This makes it possible to combine 2PA induced PDT using COF with programmed cell death protein 1 immune checkpoint blockade therapy. Such combination leads to strong abscopal tumor-inhibiting efficiency and long-lasting immune memory effects, standing as a promising combinatorial therapeutic strategy for cancer treatment.

中文翻译：

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使用共价有机框架的双光子吸收诱导癌症免疫治疗

免疫检查点阻断疗法正在彻底改变多种肿瘤类型的传统治疗模式，但对大部分患者仍然无效。光动力疗法 (PDT) 已被证明可诱导癌细胞死亡并引发免疫反应，并且可能代表一种与免疫检查点阻断疗法协同作用的潜在策略。然而，常规 PDT 激发光对组织的有限穿透在很大程度上阻碍了其在临床中的应用以及与免疫疗法的进一步结合。在这里，锯齿状堆积共价有机骨架 (COF) COF-606 具有优异的双光子吸收 (2PA) 特性和光稳定性，在很大程度上避免了聚集引起的猝灭，因此提供了高活性氧 (ROS) 生成效率；在深部肿瘤组织中用作PDT的2PA光敏剂。COF-606 诱导的 PDT 被证明在诱导免疫原性细胞死亡、引发免疫反应和首次使免疫抑制状态正常化方面是有效的。这使得将使用 COF 的 2PA 诱导的 PDT 与程序性细胞死亡蛋白 1 免疫检查点阻断疗法相结合成为可能。这种组合导致强大的远隔肿瘤抑制效率和持久的免疫记忆效应，是一种有前途的癌症治疗组合治疗策略。这使得将使用 COF 的 2PA 诱导的 PDT 与程序性细胞死亡蛋白 1 免疫检查点阻断疗法相结合成为可能。这种组合导致强大的远隔肿瘤抑制效率和持久的免疫记忆效应，是一种有前途的癌症治疗组合治疗策略。这使得将使用 COF 的 2PA 诱导的 PDT 与程序性细胞死亡蛋白 1 免疫检查点阻断疗法相结合成为可能。这种组合导致强大的远隔肿瘤抑制效率和持久的免疫记忆效应，是一种有前途的癌症治疗组合治疗策略。