铁死亡触发的免疫原性细胞死亡（ICD）被广泛用于通过催化有毒活性氧（ROS）的产生来增强人体的抗肿瘤免疫力。然而，铁死亡和免疫治疗的疗效受到细胞内丰富的谷胱甘肽（GSH）和免疫抑制的肿瘤微环境的极大限制。在此，提出了一种简便的自下而上的无溶剂合成超薄锰（Mn）基层状双氢氧化物纳米片的方法，该方法对促炎细胞因子IFNγ（IFNγ/uMn-LDH）具有高负载效率，以相互增强铁死亡和全身免疫。锰离子的引入显着促进 GSH 消耗和羟基自由基生成，这可以通过 IFNγ 递送诱导的 SLC7A11 下调进一步增强。细胞铁死亡后的 ICD 效应与 IFNγ/uMn-LDH 的内在免疫调节特性相配合，促进树突状细胞 (DC) 的成熟和 T 细胞的启动。活化的 CD8 T 细胞分泌的 IFNγ 反过来涉及级联免疫原性铁死亡，从而构建闭环疗法。值得注意的是，在原发肿瘤和远处肿瘤的生长抑制中观察到有效的远隔效应。总体而言，超薄锰基粘土纳米平台为铁死亡和抗肿瘤免疫反应之间的相互调节提供了一种简单的方法，克服了当前癌症免疫治疗的障碍。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

Ferroptosis-triggered immunogenic cell death (ICD) is widely adopted to potentiate the body's antitumor immunity by catalyzing the production of toxic reactive oxygen species (ROS). However, the efficacy of ferroptosis and immunotherapy is greatly restricted by intracellular abundant glutathione (GSH) and immunosuppressive tumor microenvironment. Herein, a facile bottom-up method for solvent-free synthesis of ultrathin manganese (Mn)-based layered double hydroxide nanosheets with high loading efficiency for pro-inflammatory cytokine IFNγ (IFNγ/uMn-LDHs) is proposed to mutually reinforce the ferroptosis and systemic immunity. The introduction of manganese ions significantly contributes to GSH depletion and hydroxyl radical generation, which can be further enhanced by IFNγ delivery induced SLC7A11 downregulation. The ICD effect after cell ferroptosis cooperates with the intrinsic immunomodulatory property of IFNγ/uMn-LDHs to facilitate the maturation of dendritic cells (DCs) and the priming of T cells. IFNγ secretion from activated CD8+ T cells in turn involves cascade immunogenic ferroptosis, thus constructing a closed-loop therapy. Remarkably, potent abscopal effect is observed in the growth inhibition of both primary and distant tumors. Overall, the ultrathin Mn-based clay nanoplatform provides a simple approach for mutual regulation between ferroptosis and antitumor immune response, overcoming the obstacles of current cancer immunotherapy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.