Nanointegrative In Situ Reprogramming of Tumor-Intrinsic Lipid Droplet Biogenesis for Low-Dose Radiation-Activated Ferroptosis Immunotherapy

Zhang, Qiqi; Wang, Xuan; Zhao, Yuanyuan; Cheng, Zhuo; Fang, De; Liu, Yingqi; Tian, Gan; Li, Menghuan; Luo, Zhong

doi:10.1021/acsnano.3c08907

Cited by 2 publications

(1 citation statement)

References 66 publications

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“…In recent years, strategies activating innate immunity for antitumor therapy have attracted much attention. − Since the enhancement of antitumor activity of cytotoxic T lymphocytes (CTLs) and the maintenance of long-term immune memory are dependent on innate immune system activation, − a critically important function of the innate immune system is to employ the phagocytic capability of innate immune cells, such as macrophages and dendritic cells (DCs), to scavenge senescent, apoptotic, and tumor cells. , However, immune escape is often associated with the expression of antiphagocytic signaling molecules by tumor cells. − CD47, , also known as integrin-associated protein, is a highly glycosylated transmembrane protein widely distributed on the surface of various tumor cells. CD47 is a “do not eat me” antiphagocytic signaling molecule, and its ligand is signal regulatory protein α (SIRPα), which is mainly expressed on the surface of phagocytic cells such as macrophages and DCs.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy

Fu,

Feng,

et al. 2024

Mol. Pharmaceutics

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The antitumor strategies based on innate immunity activation have become favored by researchers in recent years. In particular, strategies targeting antiphagocytic signaling blockade to enhance phagocytosis have been widely reported. For example, the addition of prophagocytic signals such as calreticulin could make the strategy significantly more effective. In this study, an antitumor strategy that combines photodynamic therapy (PDT) with CD47 blockade has been reported. This approach promotes the maturation of dendritic cells and the presentation of tumor antigens by PDT-mediated tumor immunogenic cell death, as well as the enhancement of cytotoxic T lymphocyte infiltration in tumor areas and the phagocytic activity of phagocytes. Furthermore, the downregulation and blockage of CD47 protein could further promote phagocytic activity, strengthen the innate immune system, and ultimately elevate the antitumor efficacy and inhibit tumor metastasis.

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Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy

Fu,

Feng,

et al. 2024

Mol. Pharmaceutics

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The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy

Mao,

Hu,

Zhao

et al. 2024

Apoptosis

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Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each. Graphical Abstract Ferroptosis in the tumor microenvironment involves intricate crosstalk between tumor cells and immune cells. Through MHC recognition, CD8+T cells activate the JAK1/STAT1 pathway in tumor cells, impairing the function of System Xc and reducing GSH and GPX4 expression to promote tumor cell ferroptosis. Additionally, activation of the STAT1-IRF1-ACSL4 pathway could also promote ferroptosis. The blockade of the antioxidant pathway in tumor cells induces ferroptosis, and the released DAMPs could promote DCs maturation through the cGAMP-STING-TBK1 pathway, leading to antigen presentation that activates CD8+T cells. The release of DAMPs also induces the M1-type polarization of macrophages, which exerts an anti-tumor effect. The anti-tumor effects of CD8+T cells could also be enhanced by blocking inhibitory immune checkpoints such as PD-1, PD-L1, CTLA4, and LAG3. Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; BH4, tetrahydrobiopterin; cGAMP, cyclic GMP-AMP; CTLA4, cytotoxic T lymphocyte-associated antigen-4; DCs, dendritic cells; DHFR, dihydrofolate reductase; DHODH, dihydroorotate dehydrogenase; GPX4, glutathione peroxidase 4; GSH, glutathione; HIF-1α, Hypoxia-Inducible Factor-1α;IFN-γ, interferon-γ; IRF1, interferon regulatory factor 1;IRP1, iron regulatory protein 1; JAK 1, janus kinase; LAG3, lymphocyte activation gene 3; MHC, major histocompatibility complex; NRF2, nuclear factor erythroid-2-related factor 2; PD-1, programmed death protein -1; PD-L1, programmed death ligand 1; PUFA, polyunsaturated fatty acid; ROS, reative oxygen species; STAT1, signal transducer and activator of transcription 1; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1 TLR2, toll-like receptor 2. This diagram was drawn by Figdraw (www.figdraw.com).

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Nanointegrative In Situ Reprogramming of Tumor-Intrinsic Lipid Droplet Biogenesis for Low-Dose Radiation-Activated Ferroptosis Immunotherapy

Cited by 2 publications

References 66 publications

Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy

Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy

The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy

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