中国科学院上海硅酸盐研究所施剑林小组，报道了铁基纳米催化剂在增强肿瘤免疫治疗中，铁死亡到焦亡的调控作用。相关论文于2024年11月12日发表在《美国化学会杂志》上。

据悉，免疫原性细胞死亡通过参与先天和适应性免疫，是增强抗肿瘤免疫治疗的关键机制。然而，一个关键的悬而未决的问题是，哪种细胞死亡模式，特别是铁死亡或焦亡，是激活免疫反应的最佳途径。

在这项研究中，该团队合成了一种创新的铁基纳米催化药物，可以策略性地调节铁死亡到焦亡，以增强抗肿瘤免疫治疗。通过利用铁与羰基氰化物间氯苯腙（CP）之间复杂的相互作用，研究团队设计了一种纳米药物，该药物能够调节肿瘤细胞内铁死亡到更具免疫原性的焦亡。

体外分析表明，与未掺入CP（只有铁）的铁基纳米药物相比，CP包封的铁基纳米药物（HFCP）可以有效诱导癌细胞焦亡，在根除肿瘤细胞和刺激免疫应答方面的效果大大增强。结果表明，HFCP不仅能有效抑制原发肿瘤的生长，还能在很大程度上抑制未治疗的远端肿瘤的生长，具有明显的诱导免疫记忆作用。

综上所述，这些结果表明HFCP诱导的焦亡相比铁亡，提供了一种更有效的肿瘤免疫治疗方法，通过逆转免疫抑制的肿瘤微环境和有效调节免疫原性细胞死亡模式，为实现长期的免疫治疗结果提供了有希望的潜力。

附：英文原文

Title: Ferroptosis to Pyroptosis Regulation by Iron-Based Nanocatalysts for Enhanced Tumor Immunotherapy

Author: Qishuai Feng, Fenggang Qi, Wenming Fang, Ping Hu, Jianlin Shi

Issue&Volume: November 12, 2024

Abstract: Immunogenic cell death serves as a pivotal mechanism in enhancing antitumor immunotherapy by engaging both innate and adaptive immune responses. However, a key unanswered question is which mode of cell death, particularly ferroptosis or pyroptosis, serves as the optimal pathway for activating the immune response. In this study, we introduce an innovative iron-based nanocatalytic medicine that strategically regulates ferroptosis to pyroptosis to augment antitumor immunotherapy. By harnessing the intricate interplay between iron and carbonyl cyanide m-chlorophenyl hydrazone (CP), we engineered the nanomedicine which is capable of regulating ferroptosis to the more immunogenic pyroptosis within tumor cells. In vitro analyses revealed that the treatment with CP-encapsulated iron-based nanomedicine (HFCP) can effectively induce pyroptosis of cancer cells, exhibiting greatly enhanced efficacy in eradicating tumor cells and stimulating immune responses compared to the ferroptosis-inducing counterpart without CP incorporation (iron alone). Resultantly, HFCP not only effectively inhibited primary tumor growth but also suppressed the growth of untreated distant tumors to a large extent, underscoring a notably induced immune memory. Taken together, these results indicate that HFCP-induced pyroptosis offers a significantly more powerful approach to tumor immunotherapy than ferroptosis, offering promising potentials for achieving long-term immunotherapeutic outcomes through the reversal of the immunosuppressive tumor microenvironment and the effective regulation of immunogenic cell death modes.

DOI: 10.1021/jacs.4c08304

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c08304