scholarly journals Chromomycin A5 induces bonafide immunogenic cell death in metastatic melanoma

2021 ◽  
Author(s):  
Katharine G. D. Florêncio ◽  
Evelline A. Edson ◽  
Francisco C. L. Pinto ◽  
Otília D. L. Pessoa ◽  
João Agostinho Machado-Neto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Metastatic Melanoma ◽  
Melanoma Cell Line ◽  
Atp Release ◽  
Immunogenic Cell Death ◽  
First Line ◽  
Metastatic Melanoma Cell ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

AbstractSome first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8). B16-F10, a metastatic melanoma cell line, treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2α and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bonafide ICD induction by CA5 was confirmed by a C57BL/6 mice vaccination assay with CA5-treated cells. These findings support a high potential of CA5 as an anticancer candidate against AMM.

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.

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...

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 Natural Melanin-Based Nanoparticles With Combined Chemo/Photothermal/Photodynamic Effect Induce Immunogenic Cell Death (ICD) on Tumor

2021 ◽  
Vol 9 ◽  
Author(s):  
Ding Liu ◽  
Huilin Huang ◽  
Bingxia Zhao ◽  
Weihong Guo
Keyword(s):  
Cell Death ◽  
Natural Product ◽  
Near Infrared ◽  
Tumor Therapy ◽  
Cell Uptake ◽  
Immunogenic Cell Death ◽  
Photodynamic Effect ◽  
Promising Agent ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Melanin, as a natural product, has been used as an extraordinary ingredient for nanomedicine due to its great biocompatibility and light responsive property. In this study, polydopamine (PDA), an analog of melanin, was extracted from dopamine and encapsulated with doxorubicin (DOX). The as-prepared nanoparticles (NPs) with good stability, great biosafety and high near infrared (NIR) responsive property ameliorated the cell uptake of DOX in OS-RC-2/ADR cells, exhibited synergistic chemo/photothermal (PTT)/photodynamic (PDT) effects, induced the release of damage associated molecular patterns (DAMPs), and finally, led to immunogenic cell death (ICD). In general, it was suggested that PDA-DOX NPs with NIR irradiation could serve as a promising agent for tumor therapy.

scholarly journals Extracellular Vesicles and DAMPs in Cancer: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Nadiah Abu ◽  
Nurul Ainaa Adilah Rus Bakarurraini ◽  
Siti Nurmi Nasir
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
External Stress ◽  
Immunogenic Cell Death ◽  
Induce Cell Death ◽  
Molecular Patterns ◽  
Inflammatory Molecules ◽  
Damage Associated Molecular Patterns

Certain cancer therapy has been shown to induce immunogenic cell death in cancer cells and may promote tumor progression instead. The external stress or stimuli may induce cell death and contribute toward the secretion of pro inflammatory molecules. The release of damage-associated molecular patterns (DAMPs) upon induction of therapy or cell death has been shown to induce an inflammatory response. Nevertheless, the mechanism as to how the DAMPs are released and engage in such activity needs further in-depth investigation. Interestingly, some studies have shown that DAMPs can be released through extracellular vesicles (EVs) and can bind to receptors such as toll-like receptors (TCRs). Ample pre-clinical studies have shown that cancer-derived EVs are able to modulate immune responses within the tumor microenvironment. However, the information on the presence of such DAMPs within EVs is still elusive. Therefore, this mini-review attempts to summarize and appraise studies that have shown the presence of DAMPs within cancer-EVs and how it affects the downstream cellular process.

scholarly journals Pyroptotic and Necroptotic Cell Death in the Tumor Microenvironment and Their Potential to Stimulate Anti-Tumor Immune Responses

2021 ◽  
Vol 11 ◽  
Author(s):  
Allan Scarpitta ◽  
Ulrich T. Hacker ◽  
Hildegard Büning ◽  
Olivier Boyer ◽  
Sahil Adriouch
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Immune Cells ◽  
Immunogenic Cell Death ◽  
Chemotherapeutic Drugs ◽  
Immune Functions ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Damage Associated Molecular Patterns

Cancer remains the second most common cause of death worldwide affecting around 10 million patients every year. Among the therapeutic options, chemotherapeutic drugs are widely used but often associated with side effects. In addition, toxicity against immune cells may hamper anti-tumor immune responses. Some chemotherapeutic drugs, however, preserve immune functions and some can even stimulate anti-tumor immune responses through the induction of immunogenic cell death (ICD) rather than apoptosis. ICD stimulates the immune system by several mechanisms including the release of damage-associated molecular patterns (DAMPs) from dying cells. In this review, we will discuss the consequences of inducing two recently characterized forms of ICD, i.e., pyroptosis and necroptosis, in the tumor microenvironment (TME) and the perspectives they may offer to increase the immunogenicity of the so-called cold tumors and to stimulate effective anti-tumor immune responses.

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