Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses

Immunological Reviews, Год журнала: 2017, Номер 280(1), С. 126 - 148

Опубликована: Окт. 13, 2017

Summary The immunogenicity of cancer cells is an emerging determinant anti‐cancer immunotherapy. Beyond developing immunostimulatory regimens like dendritic cell‐based vaccines, immune‐checkpoint blockers, and adoptive T‐cell transfer, investigators are beginning to focus on the immunobiology dying its relevance for success anticancer immunotherapies. It currently accepted that may die in response therapies through regulated cell death programs, which either repress or increase their immunogenic potential. In particular, induction ( ICD ), hallmarked by emission damage‐associated molecular patterns (DAMPs); molecules analogous pathogen‐associated (PAMPs) acting as danger signals/alarmins, great therapy. These ‐associated signals favor immunomodulatory responses lead tumor‐associated antigens (TAAs)‐directed immunity, paves way removal residual, treatment‐resistant cells. also succumbing can orchestrate “altered‐self mimicry” i.e. mimicry pathogen defense responses, levels nucleic acids and/or chemokines (resulting type I interferon/ IFN response‐like neutrophil activity). this review, we exhaustively describe main molecular, immunological, preclinical, clinical aspects immunosuppressive (with respect apoptosis, necrosis necroptosis). We provide extensive historical background these fields, with special attention self/non‐self models, have shaped field immunology.

Язык: Английский

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Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Фев. 20, 2021

Abstract Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon armory of therapy. Accumulating evidence suggests that tumor microenvironment plays a critical role anti-cancer immunity, which may result checkpoint blockade therapy being ineffective, addition to other novel immunotherapies patients. In present review, we discuss deficiencies current immunotherapies. More importantly, highlight regulators surveillance, immunological evasion, and potential for their further translation into clinical practice. Based on general targetability therapy, believe promising immunotherapeutic targets. Targeting microenvironment, alone or combination with drugs, might benefit patients future.

Язык: Английский

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SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Окт. 9, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage inflammatory cytokine storm are believed be directly associated with disease 2019 (COVID-19) clinical manifestations, underlying mechanisms of virus-triggered responses currently unknown. Here we report that SARS-CoV-2 activates caspase-8 trigger cell apoptosis processing epithelial cells. The processed cytokines released through necroptosis pathway. Virus-induced apoptosis, necroptosis, inflammation activation were also observed sections SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying pathogenesis. Furthermore, analysis postmortem fatal COVID-19 patients revealed not only but massive infiltration, necrotic debris, pulmonary interstitial fibrosis, typical immune pathogenesis lung. triggered dual mode death pathways caspase-8-dependent may These discoveries might assist development therapeutic strategies treat COVID-19.

Язык: Английский

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Necroptosis: a crucial pathogenic mediator of human disease

JCI Insight, Год журнала: 2019, Номер 4(15)

Опубликована: Авг. 7, 2019

Necroptosis is a genetically regulated form of necrotic cell death that has emerged as an important pathway in human disease. The necroptosis induced by variety signals, including receptor ligands, and receptor-interacting protein kinases 1 3 (RIPK1 RIPK3) mixed-lineage kinase domain–like pseudokinase (MLKL), which regulatory necrosome complex. RIPK3-mediated phosphorylation MLKL executes necroptosis. Recent studies, using animal models tissue injury, have revealed RIPK3 are key effectors injury propagation. This Review explores the functional roles crucial pathogenic determinants markers disease progression severity experimental disease, acute chronic pulmonary diseases; renal, hepatic, cardiovascular, neurodegenerative cancer; critical illness.

Язык: Английский

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Cell Death in the Lung: The Apoptosis–Necroptosis Axis

Annual Review of Physiology, Год журнала: 2018, Номер 81(1), С. 375 - 402

Опубликована: Ноя. 28, 2018

Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought be the only regulated mechanism; however, new modalities of caspase-independent have been identified, including necroptosis, pyroptosis, and autophagic death. As an understanding cellular mechanisms that mediate continues grow, there increasing evidence these pathways are implicated in pathogenesis many pulmonary disorders. This review summarizes our as it pertains chronic obstructive disease, asthma, idiopathic fibrosis, acute respiratory distress syndrome, arterial hypertension.

Язык: Английский

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Regulated necrosis in kidney ischemia-reperfusion injury

Kidney International, Год журнала: 2019, Номер 96(2), С. 291 - 301

Опубликована: Март 7, 2019

Язык: Английский

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Cell death in pancreatic cancer: from pathogenesis to therapy

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2021, Номер 18(11), С. 804 - 823

Опубликована: Июль 30, 2021

Язык: Английский

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Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

OncoImmunology, Год журнала: 2017, Номер 6(12), С. e1386829 - e1386829

Опубликована: Окт. 4, 2017

The expression “immunogenic cell death” (ICD) refers to a functionally unique form of death that facilitates (instead suppressing) T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation adaptive responses in dying cells, culminating with exposure or secretion immunostimulatory molecules commonly referred as “damage-associated molecular patterns”. Only few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress development ICD-inducing chemotherapeutic regimens, focusing studies evaluate clinical efficacy conjunction immunological biomarkers.

Язык: Английский

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Cell death mechanisms in eukaryotes

Cell Biology and Toxicology, Год журнала: 2019, Номер 36(2), С. 145 - 164

Опубликована: Дек. 9, 2019

Язык: Английский

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Programmed Cell Death Tunes Tumor Immunity

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 30, 2022

The demise of cells in various ways enables the body to clear unwanted cells. Studies over years revealed distinctive molecular mechanisms and functional consequences several key cell death pathways. Currently, most intensively investigated programmed (PCD) includes apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis, autophagy, which has been discovered play crucial roles modulating immunosuppressive tumor microenvironment (TME) determining clinical outcomes cancer therapeutic approaches. PCD can dual roles, either pro-tumor or anti-tumor, partly depending on intracellular contents released during process. also regulates enrichment effector regulatory immune cells, thus participating fine-tuning anti-tumor immunity TME. In this review, we focused primarily discussed messengers regulating their intricate crosstalk with response TME, explored immunological consequence its implications future therapy developments.

Язык: Английский

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