Immunogenic cell stress and death

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 487 - 500

Published: Feb. 10, 2022

Language: Английский

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Detection of immunogenic cell death and its relevance for cancer therapy

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(11)

Published: Nov. 26, 2020

Abstract Chemotherapy, radiation therapy, as well targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by exposure release numerous damage-associated molecular patterns (DAMPs), altogether confer a robust adjuvanticity dying cancer cells, they favor recruitment activation antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) secreted ATP, annexin A1 (ANXA1), type I interferon, high-mobility group box 1 (HMGB1). Additional hallmarks ICD encompass phosphorylation eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known eIF2α), autophagy, global arrest in transcription translation. Here, we outline methodological approaches for measuring markers vitro ex vivo discovery next-generation antineoplastic agents, development personalized regimens, identification optimal therapeutic combinations clinical management cancer.

Language: Английский

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Autophagy in inflammation, infection, and immunometabolism

Immunity, Journal Year: 2021, Volume and Issue: 54(3), P. 437 - 453

Published: March 1, 2021

Language: Английский

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Mitochondrial control of inflammation

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 159 - 173

Published: July 25, 2022

Language: Английский

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Ferroptosis in infection, inflammation, and immunity

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(6)

Published: May 12, 2021

Ferroptosis is a type of regulated necrosis that triggered by combination iron toxicity, lipid peroxidation, and plasma membrane damage. The upstream inducers ferroptosis can be divided into two categories (biological versus chemical) activate major pathways (the extrinsic/transporter the intrinsic/enzymatic pathways). Excessive or deficient ferroptotic cell death implicated in growing list physiological pathophysiological processes, coupled to dysregulated immune response. This review focuses on new discoveries related how cells their spilled contents shape innate adaptive immunity health disease. Understanding immunological characteristics activity not only illuminates an intersection between but may also lead development novel treatment approaches for immunopathological diseases.

Language: Английский

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From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 4641 - 4657

Published: Jan. 1, 2021

Pyroptosis, apoptosis and necroptosis are the most genetically well-defined programmed cell death (PCD) pathways, they intricately involved in both homeostasis disease. Although identification of key initiators, effectors executioners each these three PCD pathways has historically delineated them as distinct, growing evidence highlighted extensive crosstalk among them. These observations have led to establishment concept PANoptosis, defined an inflammatory pathway regulated by PANoptosome complex with features pyroptosis, and/or that cannot be accounted for any alone. In this review, we provide a brief overview research history necroptosis. We then examine intricate discuss current PANoptosis. also detail molecular assembly complex, scaffold contemporaneous engagement molecules from apoptosis, PANoptosis is now known critically many diseases, including infection, sterile inflammation cancer, future discovery novel PANoptotic components will continue broaden our understanding fundamental processes inform development new therapeutics.

Language: Английский

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The cGAS–STING pathway and cancer

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(12), P. 1452 - 1463

Published: Dec. 12, 2022

Language: Английский

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Macrophages: The Good, the Bad, and the Gluttony

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 12, 2021

Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile interpret recent findings on plasticity macrophages how these contribute to development non-infectious inflammatory diseases, with a particular focus allergic autoimmune disorders. The inflammation then be examined, emphasizing ability clear apoptotic immune cells. Rheumatoid arthritis (RA) is chronic autoimmune-driven spectrum diseases where persistent results synovial hyperplasia excessive cell accumulation, leading remodeling reduced function affected joints. central pathophysiology RA, driving episodic cycles tissue destruction. RA patients have increased numbers active M1 polarized pro-inflammatory few or inactive M2 type This imbalance macrophage homeostasis main contributor mediators resulting continual activation stromal populations accelerated remodeling. Modulation phenotype remains key therapeutic goal for treatment disease. Intriguingly, intervention glucocorticoids other DMARDs promotes re-polarization an anti-inflammatory phenotype; reprogramming dependent metabolic changes promote phenotypic switching. Allergic asthma associated Th2-polarised airway inflammation, structural large airways, hyperresponsiveness. Macrophage polarization has profound impact pathogenesis, as response allergen exposure regulated by intricate interplay between local factors including cytokines, chemokines danger signals from neighboring Th2-polarized environment characteristic asthma, high levels IL-4 produced locally infiltrating innate lymphoid helper T acquisition alternatively activated M2a macrophages, myriad effects structure. Targeting regulators currently being pursued diseases. re-balancing responses towards pro-resolution thus success response. It long been established apoptosis supports monocyte recruitment sites facilitating subsequent corpse clearance. drives mediates switch polarity macrophages. However, role cell-derived extracellular vesicles (ACdEV) control received remarkably little attention. ACdEV powerful intercellular communication, carrying wealth lipid protein may modulate phenotype, cargo immune-modulating enzymes. such interactions result repair disease different contexts. discuss origin, characterization, activity underlying mechanisms via clearance, order provide new insights into strategies could exploit capabilities agile responsive

Language: Английский

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Modes of Regulated Cell Death in Cancer

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(2), P. 245 - 265

Published: Jan. 18, 2021

Cell suicide pathways, termed regulated cell death (RCD), play a critical role in organismal development, homeostasis, and pathogenesis. Here, we provide an overview of key RCD modalities, namely apoptosis, entosis, necroptosis, pyroptosis, ferroptosis. We explore how various modules serve as defense mechanism against the emergence cancer well manner which they can be exploited to drive oncogenesis. Furthermore, outline current therapeutic agents that activate consider novel RCD-based strategies for tumor elimination. SIGNIFICANCE: A variety antitumor therapeutics eliminate cells by harnessing devastating potential cellular emphasizing importance battling cancer. This review supplies mechanistic perspective distinct modalities explores important tumorigenesis. discuss double-edged sword approaches aimed at selectively manipulating eradication.

Language: Английский

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The Apoptosis Paradox in Cancer

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1328 - 1328

Published: Jan. 25, 2022

Cancer growth represents a dysregulated imbalance between cell gain and loss, where the rate of proliferating mutant tumour cells exceeds those that die. Apoptosis, most renowned form programmed death, operates as key physiological mechanism limits population expansion, either to maintain tissue homeostasis or remove potentially harmful cells, such have sustained DNA damage. Paradoxically, high-grade cancers are generally associated with high constitutive levels apoptosis. In cancer, cell-autonomous apoptosis constitutes common suppressor mechanism, property which is exploited in cancer therapy. By contrast, limited tumour-cell also has potential promote survival resistance therapy by conditioning microenvironment (TME)-including phagocytes viable cells-and engendering pro-oncogenic effects. Notably, apoptosis-mediated activation innate immune system can help orchestrate TME may effect evasion treatment. Here, we present an overview implications death programmes biology, particular focus on process "double-edged" consequences: one hand, being suppressive through deletion malignant pre-malignant while, other, progressive stimulation reparatory regenerative responses TME.

Language: Английский

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