冷冻消融和免疫疗法相结合提供了一种恢复实体瘤免疫抑制反应的有前途的方法。然而，诸如消融后残留肿瘤和免疫活性不足等挑战会导致冷冻免疫治疗后的复发。在此，我们研究了金属超结构低温纳米催化剂（MSCN），其具有大量冰成核位点和治疗剂的间隙负载。 MSCN 提高冰点并增强冰成核，促进冷冻处理过程中有效的冰形成。装载MSCN的肿瘤细胞的低温细胞毒性增加了2倍，并经历渗透相关的细胞损伤，主要是坏死性凋亡，而不是其他受调节的细胞死亡机制。在前列腺癌模型中，RNA 测序表明，与单独冷冻消融相比，MSCN 冷冻消融促进了抗肿瘤炎症途径，包括坏死性凋亡。此外，冷冻消融后程序性死亡配体 1 (PD-L1) 上调后，证实了与 PD-L1 阻断的协同作用。考虑到用于 aPD-L1 负载的 MSCN 间隙，我们将 PD-L1 阻断剂的瘤内递送与全身注射进行比较。 MSCN 冷冻消融和 PD-L1 阻断增强的坏死和坏死性凋亡有效地根除肿瘤，并引发局部和全身的抗肿瘤和记忆免疫反应。最后，分析肿瘤浸润免疫细胞的空间景观，以深入了解异质性肿瘤反应，从而解决传统局灶消融技术的局限性。我们的研究结果强调了使用冷冻纳米催化的先进冷冻免疫疗法促进冰形成和坏死性凋亡、刺激抗肿瘤免疫原性反应的潜力。

Combining cryoablation and immunotherapy presents a promising approach to revert immunosuppressive responses to solid tumors. However, challenges such as postablated residual tumors and insufficient immune activity contribute to recurrence after cryo-immunotherapy. Herein, we investigated metallic supra-structured cryo-nanocatalyst (MSCN), which features numerous ice nucleation sites and interspace loading of therapeutic agents. MSCN elevates the freezing point and enhances ice nucleation, facilitating effective ice formation during cryotreatment. MSCN-loaded tumor cells showed a 2-fold increase in cryo-cytotoxicity and undergo osmotic-related cell damage, primarily necroptosis rather than other regulated cell death mechanisms. In prostate cancer models, RNA sequencing reveals that MSCN-cryoablation promoted antitumor inflammatory pathways, including necroptosis, compared to cryoablation alone. Additionally, following programmed death-ligand 1 (PD-L1) upregulation postcryoablation, synergistic effects with PD-L1 blockade were confirmed. Given the interspace of MSCN for aPD-L1 loading, we compared the intratumoral delivery of PD-L1 blockade against systemic injection. Enhanced necrosis and necroptosis from MSCN-cryoablation and PD-L1 blockade effectively eradicated tumors and triggered antitumor and memory immune responses locally and systemically. Lastly, a spatial landscape of tumor-infiltrating immune cells was analyzed to gain insight into heterogeneous tumor responses, leading to the limitations of conventional focal ablation techniques. Our findings highlight the potential of advanced cryo-immunotherapy using cryo-nanocatalysis to promote ice formation and necroptosis, stimulating antitumor immunogenic responses.