A Photoactivated Ir(III) Complex Targets Cancer Stem Cells and Induces Secretion of Damage-associated Molecular Patterns in Melamoma Cells Characteristic of Immunogenic Cell Death

2021 ◽  
Author(s):  
Gloria Vigueras ◽  
Lenka Markova ◽  
Vojtech Novohradsky ◽  
Alicia Marco ◽  
Natalia Cutillas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Immunogenic Cell Death ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Several anticancer chemotherapies, while eliminating the bulk of tumor cells, often fail, as they do not obliterate a small fraction of malignant cancer stem cells (CSCs). Thus, developing chemotherapeutics capable...

scholarly journals Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2566
Author(s):  
María Julia Lamberti ◽  
Annunziata Nigro ◽  
Vincenzo Casolaro ◽  
Natalia Belén Rumie Vittar ◽  
Jessica Dal Col
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Current Status ◽  
Immunogenic Cell Death ◽  
Basal Expression ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

scholarly journals Biomarkers of Radiotherapy-Induced Immunogenic Cell Death

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 930
Author(s):  
Rianne D. W. Vaes ◽  
Lizza E. L. Hendriks ◽  
Marc Vooijs ◽  
Dirk De Ruysscher
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immunogenic Cell Death ◽  
Type I ◽  
Future Studies ◽  
Regulated Cell Death ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Potential Biomarkers

Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I interferon (IFN-I) responses. In recent years, intensive research has unraveled major mechanistic aspects of RT-induced ICD and has resulted in the identification of immunogenic factors that are released by irradiated tumor cells. However, so far, only a limited number of studies have searched for potential biomarkers that can be used to predict if irradiated tumor cells undergo ICD that can elicit an effective immunogenic anti-tumor response. In this article, we summarize the available literature on potential biomarkers of RT-induced ICD that have been evaluated in cancer patients. Additionally, we discuss the clinical relevance of these findings and important aspects that should be considered in future studies.

The inducers of immunogenic cell death for tumor immunotherapy

2018 ◽  
Vol 104 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Xiuying Li
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Chemotherapeutic Agents ◽  
Oncolytic Viruses ◽  
Treatment Modalities ◽  
Immunogenic Cell Death ◽  
Effective Immune Response ◽  
Promising Treatment ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Immunotherapy is a promising treatment modality that acts by selectively harnessing the host immune defenses against cancer. An effective immune response is often needed to eliminate tumors following treatment which can trigger the immunogenicity of dying tumor cells. Some treatment modalities (such as photodynamic therapy, high hydrostatic pressure or radiotherapy) and agents (some chemotherapeutic agents, oncolytic viruses) have been used to endow tumor cells with immunogenicity and/or increase their immunogenicity. These treatments and agents can boost the antitumor capacity by inducing immune responses against tumor neoantigens. Immunogenic cell death is a manner of cell death that can induce the emission of immunogenic damage-associated molecular patterns (DAMPs). DAMPs are sufficient for immunocompetent hosts to trigger the immune system. This review focuses on the latest developments in the treatment modalities and agents that can induce and/or enhance the immunogenicity of cancer cells.

scholarly journals Harnessing Natural Products of Marine Origin for Induction of Immunogenic Cell Death

2021 ◽  
pp. 1-9
Author(s):  
Manikanda Raja Keerthi Raja ◽  
Kaylee Chen ◽  
Manikanda Raja Keerthi Raja
Keyword(s):  
Cell Death ◽  
Side Effects ◽  
Tumor Cells ◽  
Immunogenic Cell Death ◽  
Marine Origin ◽  
Anti Cancer ◽  
Immune Therapies ◽  
Bona Fide ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Conventional cancer chemotherapy aims to kill highly proliferating tumor cells and is often immunosuppressive due to its off-target side effects. However, certain cytotoxic cancer chemotherapeutic drugs can kill tumor cells by triggering immunogenic cell death (ICD). Cells undergoing ICD release damage-associated molecular patterns (DAMPs) to activate robust innate and adaptive anti-tumor immune responses. Despite many compounds being able to trigger one or two hallmarks of ICD, very few bona fide ICD inducers are available. Identification of bioactive natural ICD inducers with low side effects and high tolerability represents a priority in biomedical research. In this review, we discuss the various strategies to regulate the hallmarks of ICD and enhance immunogenic potentials. We focus on evaluating the potential of natural compounds of marine origin to amplify the effects of ICD and therefore serve as novel therapeutic anti-cancer agents alone or in combination with existent chemo- or immune-therapies.

scholarly journals Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 130
Author(s):  
Michal Kielbik ◽  
Izabela Szulc-Kielbik ◽  
Magdalena Klink
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Ovarian Cancer Cells ◽  
Immunogenic Cell Death ◽  
Antigen Presenting ◽  
Molecular Patterns

Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant disease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients.

scholarly journals Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum‐Targeting Copper(II) Complex

ChemBioChem ◽  
2020 ◽  
Vol 21 (24) ◽  
pp. 3618-3624 ◽  
Author(s):  
Pooja Kaur ◽  
Alice Johnson ◽  
Joshua Northcote‐Smith ◽  
Chunxin Lu ◽  
Kogularamanan Suntharalingam
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Cancer Stem Cells ◽  
Immunogenic Cell Death ◽  
Breast Cancer Stem Cells ◽  
Endoplasmic Reticulum Targeting

scholarly journals Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Wei Yang ◽  
Zenghe Xiu ◽  
Yuping He ◽  
Wenpeng Huang ◽  
Yanyan Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Tumor Regression ◽  
Critical Role ◽  
Glioma Stem Cells ◽  
High Dose ◽  
Immunogenic Cell Death ◽  
Radiation Induced ◽  
High Doses ◽  
Molecular Patterns

Abstract Tumor regression in sites distant to the irradiated field are thought to be associated with emission of damage-associated molecular patterns (DAMPs) molecules and generation of immunogenic cell death (ICD). Glioma stem cells (GSCs) are resistant to high doses of radiation, and ultimately select the outgrowth of a more aggressive tumor. This study showed high-dose IR triggered fewer DAMPs molecules exposure and release in GSCs comparing to matched non-GSCs. Downregulation of binding immunoglobulin protein (Bip) promoted IR-mediated endoplasmic reticulum stress to generate DAMPs molecules by PERK and IRE1-α phosphorylation, and increased dendritic cells mature and effector T lymphocytes activation. GSCs treated with Bip knockdown and IR efficiently prevented tumor generation, and reduced post-radiotherapy tumor recurrence. These data suggest that Bip plays a critical role in inhibition of IR-induced ICD in GSCs, and Bip inhibition may be a promising strategy on adjuvant therapy by ameliorating tumor immune microenvironment.

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