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 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.

Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells

2011 ◽  
Vol 41 (10) ◽  
pp. 3028-3039 ◽  
Author(s):  
Kirsten Kübler ◽  
Carola tho Pesch ◽  
Nadine Gehrke ◽  
Soheila Riemann ◽  
Juliane Daßler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Nk Cells ◽  
Cancer Cells ◽  
Myeloid Cell ◽  
Cell Maturation ◽  
Poly I:C ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Immunogenic Cell Death

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.

Rediscovery of Nanoparticle-based Therapeutics: Boosting Immunogenic Cell Death for Potential Application in Cancer Immunotherapy

2021 ◽  
Author(s):  
Suah Yang ◽  
In-Cheol Sun ◽  
Hee Sook Hwang ◽  
Man Kyu Shim ◽  
Hong Yeol Yoon ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Cancer Immunotherapy ◽  
Potential Application ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Living Body ◽  
Adaptive Immune ◽  
Physical Stimuli ◽  
Molecular Patterns

Immunogenic cell death (ICD) occurred by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through releasing danger-associated molecular patterns...

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.

Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Chen ◽  
PH Wang ◽  
SS Chen ◽  
CC Wen ◽  
YH Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Dendritic Cell ◽  
Tumor Cells ◽  
Cancer Vaccine ◽  
Immunogenic Cell Death

scholarly journals Combination of Niraparib, Cisplatin and Twist Knockdown in Cisplatin-Resistant Ovarian Cancer Cells Potentially Enhances Synthetic Lethality through ER-Stress Mediated Mitochondrial Apoptosis Pathway

2021 ◽  
Vol 22 (8) ◽  
pp. 3916
Author(s):  
Entaz Bahar ◽  
Ji-Ye Kim ◽  
Dong-Chul Kim ◽  
Hyun-Soo Kim ◽  
Hyonok Yoon
Keyword(s):  
Ovarian Cancer ◽  
Cell Culture ◽  
Cell Death ◽  
Er Stress ◽  
Cisplatin Resistance ◽  
Cross Resistance ◽  
Ovarian Cancer Cells ◽  
Apoptosis Pathway ◽  
Platinum Based Chemotherapy

Poly (ADP-ribose) polymerase 1 inhibitors (PARPi) are used to treat recurrent ovarian cancer (OC) patients due to greater survival benefits and minimal side effects, especially in those patients with complete or partial response to platinum-based chemotherapy. However, acquired resistance of platinum-based chemotherapy leads to the limited efficacy of PARPi monotherapy in most patients. Twist is recognized as a possible oncogene and contributes to acquired cisplatin resistance in OC cells. In this study, we show how Twist knockdown cisplatin-resistant (CisR) OC cells blocked DNA damage response (DDR) to sensitize these cells to a concurrent treatment of cisplatin as a platinum-based chemotherapy agent and niraparib as a PARPi on in vitro two-dimensional (2D) and three-dimensional (3D) cell culture. To investigate the lethality of PARPi and cisplatin on Twist knockdown CisR OC cells, two CisR cell lines (OV90 and SKOV3) were established using step-wise dose escalation method. In addition, in vitro 3D spheroidal cell model was generated using modified hanging drop and hydrogel scaffolds techniques on poly-2-hydroxylethly methacrylate (poly-HEMA) coated plates. Twist expression was strongly correlated with the expression of DDR proteins, PARP1 and XRCC1 and overexpression of both proteins was associated with cisplatin resistance in OC cells. Moreover, combination of cisplatin (Cis) and niraparib (Nira) produced lethality on Twist-knockdown CisR OC cells, according to combination index (CI). We found that Cis alone, Nira alone, or a combination of Cis+Nira therapy increased cell death by suppressing DDR proteins in 2D monolayer cell culture. Notably, the combination of Nira and Cis was considerably effective against 3D-cultures of Twist knockdown CisR OC cells in which Endoplasmic reticulum (ER) stress is upregulated, leading to initiation of mitochondrial-mediated cell death. In addition, immunohistochemically, Cis alone, Nira alone or Cis+Nira showed lower ki-67 (cell proliferative marker) expression and higher cleaved caspase-3 (apoptotic marker) immuno-reactivity. Hence, lethality of PARPi with the combination of Cis on Twist knockdown CisR OC cells may provide an effective way to expand the therapeutic potential to overcome platinum-based chemotherapy resistance and PARPi cross resistance in OC.

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