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Immunogenic Cell Stress and Death Sensitize Tumors to Immunotherapy.

The efficacy of chemotherapy with cytotoxicants and that of targeted therapies with more sophisticated agents is limited due to the plasticity of malignant cells, which leads to the inevitable development of resistance [...].

Cellular cytotoxicity is a form of immunogenic cell death.

BACKGROUND: The immune response to cancer is often conceptualized with the cancer immunity cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or natural killer (NK) lymphocytes, is actually immunogenic currently remains unknown. METHODS: In this study, tumor cells were killed by antigen-specific T-cell receptor (TCR) transgenic CD8 T cells or activated NK cells. Immunogenic cell death …

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.

The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under precli…

Membranolytic peptide programs immunogenic cell death for cancer therapy.

A rational design for facilitating innovative cell death modes can substantially aid advances in antitumour therapy1,2. Here we design and implement a unique mode of immunogenic membranolytic cell death (mLCD) in tumour cells, characterized by time-lagged rupture from the lysosomal to plasma membranes; this approach was found to robustly potentiate immune checkpoint blockade therapy. This mode of mLCD was induced by the synthetic-acid-responsive membranolytic peptide (aMP) aMPC16-CA50, which exhibits hierarchical responsiveness to the decreasing pH associated with the tumour extracellular envi

Silver nanoparticle induced immunogenic cell death can improve immunotherapy.

Cancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift … S) and significantly increased cytokine production. The induced toxicity resulted in a shift of the immunogenic cell death (ICD) marker calreticulin to the cell surface in vitro and in vivo. Subcutaneous Renca tumors were treated with anti-PD1 or in combination with Ag-citrate-5 nm. The combination group resulted in significant reduction in tumor size, increased necrosi …

Immunogenic cell stress and death in the treatment of cancer.

The successful treatment of oncological malignancies which results in long-term disease control or the complete eradication of cancerous cells necessitates the onset of adaptive immune responses targeting tumor-specific antigens. Such desirable anticancer immunity can be triggered via the induction of immunogenic cell death (ICD) of cancer cells, thus converting malignant cells into an in situ vaccine that elicits T cell mediated adaptive immune responses and establishes durable immunological memory. The exploration of ICD for cancer treatment has been subject to extensive research. However, f…

IL6/IL10/TLR4 Govern Immunogenic Cell Death in Aortic Dissection.

BACKGROUND: Aortic dissection (AD), a life-threatening cardiovascular emergency, poses a significant threat to global cardiovascular health. … R4 as central regulators of PCD-mediated AD pathogenesis, implicating immune-vascular crosstalk and immunogenic cell death as therapeutic entry points. The identified biomarker network and drug candidates provide a translational framework for developing precision therapies against AD.

Immunogenic cell death in CNS diseases: From bench to bedside.

The central nervous system (CNS) harbors a distinct immune memory programming system, wherein immunogenic cell death (ICD) acts as a pivotal signaling hub. A spectrum of insults, from systemic metabolic dysfunction to local protein aggregation and ionic dyshomeostasis, can provoke ICD in neurons, glia, and resident immune cells. This process orchestrates the release of damage-associated molecular patterns (DAMPs) from distinct subcellular compartments. These DAMPs synergistically initiate both innate trained immunity (TI), characterized by profound metabolic-epigenetic reprogramming, and antig…

Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death.

Sertraline and indatraline are two antidepressants that function as serotonin reuptake inhibitors and have demonstrated promising anticancer potential, although their precise mechanisms of action remain unclear. Both compounds trigger cholesterol accumulation within lysosomes followed by lysosomal membrane permeabilization, ultimately leading to the activation of immunogenic cell death (ICD). This, in turn, triggers a T cell-mediated adaptive immune response that facilitates significant tumor control.

Lysosomal damage due to cholesterol accumulation triggers immunogenic cell death.

Cholesterol serves as a vital lipid that regulates numerous physiological processes. Nonetheless, its role in regulating cell death processes remains incompletely understood. In this study, we investigated the role of cholesterol trafficking in immunogenic cell death. Through cell-based drug screening, we identified two antidepressants, sertraline and indatraline, as potent inducers of the nuclear translocation of TFEB (transcription factor EB). Activation of TFEB was mediated through the autophagy-independent lipidation of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). Both com…

Research progress in inducing immunogenic cell death of tumor cells.

Immunogenic cell death (ICD) is a regulated cell death (RCD) pathway. In response to physical and chemical signals, tumor cells activate specific signaling pathways that stimulate stress responses in the endoplasmic reticulum (ER) and expose damage-associated molecular patterns (DAMPs), which promote antitumor immune responses. As a result, the tumor microenvironment is altered, and many tumor cells are killed. The ICD response in tumor cells requires inducers. These inducers can be from different sources and contribute to the development of the ICD either indirectly or directly. The combinati…

Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation.

Innovative strategies to re-establish the immune-mediated destruction of malignant cells is paramount to the success of anti-cancer therapy. Accumulating evidence suggests that radiotherapy and select chemotherapeutic drugs and small molecule inhibitors induce immunogenic cell stress on tumors that results in improved immune recognition and targeting of the malignant cells. Through immunogenic cell death, which entails the release of antigens and danger signals, and immunogenic modulation, wherein the phenotype of stressed cells is altered to become more susceptible to immune attack, radiother…

Активировать новый способ смерти клеток, чтобы убить ПИ-стойкую миелому и усилить иммуногенную смерть клеток.

Стойкость к протеиновым ингибиторам (ИП) и недостаточное использование иммунитета против опухоли по-прежнему являются основными препятствиями для эффективного лечения множественной миеломы (ММ). Здесь мы идентифицировали биоактивный естественный продукт авулиганна как перспективный в переводе агент, который сохраняет активность в клетках MM, устойчивых к PI, и поощряет иммунную реакцию против миломы. Anwulignan продемонстрировал мощную цитотоксичную активность против клеток MM и продемонстрировал мощный синергетический эффект с протеаозными ингибиторами как in vitro, так и in vivo. В моделях M

Совпадение в аннотации оригинала
Resistance to proteasome inhibitors (PIs) and inadequate engagement of anti-tumor immunity remain major barriers to effective treatment of m … wulignan activated the caspase-1-dependent gasdermin D (GSDMD) pyroptosis pathway, thereby inducing immunogenic cell death. Genetic silencing of GSDMD markedly impaired anwulignan-mediated tumor suppression in vitro and in vivo, highlighting pyroptosis as a critical effector mechanism. In immunocompetent syngeneic MM models, anwulignan treatment increased bone marrow an …

BET bromodomain inhibitor JQ1 promotes immunogenic cell death in tongue squamous cell carcinoma.

Drug resistance substantially limits the curative capability of chemotherapy in head and neck cancers such as oral squamous cell carcinoma. Immunosuppression is considered a potential cause of drug resistance. A key discovery in the past decade is that chemotherapeutics can alter tumor cell immunogenicity via inducing release of damage-associated molecular patterns (DAMPs), including ecto-calreticulin (ecto-CALR), high mobility group box 1 (HMGB1) and ATP, causing tumor cells to die in a manner known as bona fide immunogenic apoptosis or immunogenic cell death (ICD). Intriguingly, JQ1 was foun…

Oncolytic Virotherapy and Immunogenic Cell Death: Mechanisms, Platforms, and Clinical Translation.

Oncolytic viruses represent a paradigm-shifting approach to cancer immunotherapy, functioning as in situ vaccines that convert immunologically "cold" tumors into "hot" tumors through induction of immunogenic cell death (ICD). Despite the clinical success of checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), many patients exhibit primary or acquired resistance due to insufficient tumor immunogenicity and exclusion of tumor-infiltrating lymphocytes. Oncolytic viruses address this limit…

Quercetin induces immunogenic cell death against gastric cancer by targeting NR3C1.

Gastric cancer is a major global health issue with limited treatment options. Quercetin, a natural flavonoid, has shown anticancer effects, but its mechanisms and molecular targets in gastric cancer remain unclear. This study aims to evaluate the impact of Quercetin on gastric cancer cells, focusing on its potential target, nuclear receptor subfamily 3 group C member 1 (NR3C1). AGS and MKN45 gastric cancer cells were treated with Quercetin, and cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, and immunogenic cell death (ICD) were assessed using standard assays. Phar…

Immunogenic cell death-based cancer vaccines: promising prospect in cancer therapy.

Tumor immunotherapy is a promising approach for addressing the limitations of conventional tumor treatments, such as chemotherapy and radiotherapy, which often have side effects and fail to prevent recurrence and metastasis. However, the effectiveness and sustainability of immune activation in tumor immunotherapy remain challenging. Tumor immunogenic cell death, characterized by the release of immunogenic substances, damage associated molecular patterns (DAMPs), and tumor associated antigens, from dying tumor cells (DTCs), offers a potential solution. By enhancing the immunogenicity of DTCs th…

Immunogenic cell death as driver of autoimmunity in granulomatosis with polyangiitis.

Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (i.e., phagocytosis of apoptotic neutrophils by macrophages

Dual-Stimuli-Driven Calcium Nanomachines for NO-Induced Immunogenic Cell Death.

Tumor blood vascular endothelial cells targeting has emerged as a powerful strategy to enhance the accumulation and penetration of nanomedic … e into tumor region, and are efficiently internalized by 4T1 cells. Robust tumor cell apoptosis and immunogenic cell death (ICD) can be achieved as well as efficient immune activation. Meanwhile, these calcium nanomachines can also greatly inhibit 4T1 lung metastasis and demonstrate significant efficacy against large tumors. This work offers a great opportunity for the …

Immunogenic cell death: synergizing ferroptosis and cuproptosis to overcome immunotherapy resistance.

The advent of immune checkpoint inhibitors has fundamentally changed the face of oncology, but the prevalence of primary and acquired resist … is, i.e. ferroptosis, and the recently characterized cuproptosis, have emerged as potent drivers of immunogenic cell death. This review represents a comprehensive synthesis of the molecular mechanisms that control these metal-dependent lethal cascades, which includes a detailed account of the biochemical divergence of the iron-dependent Fenton chemistry versus the coppe …