scholarly journals Immunogenic ferroptosis and where to find it?

2021 ◽  
Vol 9 (12) ◽  
pp. e003430
Author(s):  
Robin Demuynck ◽  
Iuliia Efimova ◽  
Faye Naessens ◽  
Dmitri V Krysko
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Antitumor Immunity ◽  
Anticancer Therapy ◽  
Oxidized Lipids ◽  
Immunogenic Cell Death ◽  
Cross Presentation ◽  
Regulated Cell Death ◽  
Potential Use

Ferroptosis is a recently discovered form of regulated cell death that is morphologically, genetically, and biochemically distinct from apoptosis and necroptosis, and its potential use in anticancer therapy is emerging. The strong immunogenicity of (early) ferroptotic cancer cells broadens the current concept of immunogenic cell death and opens up new possibilities for cancer treatment. In particular, induction of immunogenic ferroptosis could be beneficial for patients with cancers resistant to apoptosis and necroptosis. However, ferroptotic cancer cells may be a rich source of oxidized lipids, which contribute to decreased phagocytosis and antigen cross-presentation by dendritic cells and thus may favor tumor evasion. This could explain the non-immunogenicity of late ferroptotic cells. Besides the presence of lactate in the tumor microenvironment, acidification and hypoxia are essential factors promoting ferroptosis resistance and affecting its immunogenicity. Here, we critically discuss the crucial mediators controlling the immunogenicity of ferroptosis that modulate the induction of antitumor immunity. We emphasize that it will be necessary to also identify the tolerogenic (ie, immunosuppressive) nature of ferroptosis, which can lead to tumor evasion.

scholarly journals Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity

2020 ◽  
Vol 8 (2) ◽  
pp. e001369 ◽  
Author(s):  
Iuliia Efimova ◽  
Elena Catanzaro ◽  
Louis Van der Meeren ◽  
Victoria D Turubanova ◽  
Hamida Hammad ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Antitumor Immunity ◽  
High Mobility ◽  
Adaptive Immune System ◽  
Immunogenic Cell Death ◽  
Term Survival ◽  
Atomic Force

BackgroundImmunotherapy represents the future of clinical cancer treatment. The type of cancer cell death determines the antitumor immune response and thereby contributes to the efficacy of anticancer therapy and long-term survival of patients. Induction of immunogenic apoptosis or necroptosis in cancer cells does activate antitumor immunity, but resistance to these cell death modalities is common. Therefore, it is of great importance to find other ways to kill tumor cells. Recently, ferroptosis has been identified as a novel, iron-dependent form of regulated cell death but whether ferroptotic cancer cells are immunogenic is unknown.MethodsFerroptotic cell death in murine fibrosarcoma MCA205 or glioma GL261 cells was induced by RAS-selective lethal 3 and ferroptosis was analyzed by flow cytometry, atomic force and confocal microscopy. ATP and high-mobility group box 1 (HMGB1) release were detected by luminescence and ELISA assays, respectively. Immunogenicity in vitro was analyzed by coculturing of ferroptotic cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and activation/maturation of BMDCs (CD11c+CD86+, CD11c+CD40+, CD11c+MHCII+, IL-6, RNAseq analysis). The tumor prophylactic vaccination model in immune-competent and immune compromised (Rag-2−/−) mice was used to analyze ferroptosis immunogenicity.ResultsFerroptosis can be induced in cancer cells by inhibition of glutathione peroxidase 4, as evidenced by confocal and atomic force microscopy and inhibitors’ analysis. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2−/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells.ConclusionsThese results pave the way for the development of new therapeutic strategies for cancers based on induction of ferroptosis, and thus broadens the current concept of immunogenic cell death and opens the door for the development of new strategies in cancer immunotherapy.

The Association of Vitamins C and K3 Kills Cancer Cells Mainly by Autoschizis, a Novel Form of Cell Death. Basis of Their Potential Use as Coadjuvants in Anticancer Therapy

ChemInform ◽  
2003 ◽  
Vol 34 (33) ◽  
Author(s):  
Julien Verrax ◽  
Julie Cadrobbi ◽  
Marianne Delvaux ◽  
James M. Jamison ◽  
Jacques Gilloteaux ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Therapy ◽  
Potential Use

scholarly journals First-in-class ruthenium anticancer drug (KP1339/IT-139) induces an immunogenic cell death signature in colorectal spheroids in vitro

Metallomics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1044-1048 ◽  
Author(s):  
Debora Wernitznig ◽  
Konstantinos Kiakos ◽  
Giorgia Del Favero ◽  
Nathalie Harrer ◽  
Herwig Machat ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Drug ◽  
Antitumor Immunity ◽  
3D Model ◽  
Ruthenium Complex ◽  
Immunogenic Cell Death ◽  
First Time

ICD enhances antigenicity from dying cancer cells, which leads to antitumor immunity. We show for the first time that a ruthenium-complex induces the ICD signature in a 3D model.

The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy

2003 ◽  
Vol 38 (5) ◽  
pp. 451-457 ◽  
Author(s):  
Julien Verrax ◽  
Julie Cadrobbi ◽  
Marianne Delvaux ◽  
James M. Jamison ◽  
Jacques Gilloteaux ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Therapy ◽  
Potential Use

scholarly journals Induction of Triple-negative Breast Cancer Cells to Immunogenic Cell Death and Increase Cross-Presentation by Streptomyces sanyensis

2021 ◽  
Vol 13 (3) ◽  
pp. 165-172
Author(s):  
Xingguo Quan ◽  
Ji-Young Lee ◽  
Jin Hee Park ◽  
Md. Masudul Haque ◽  
Hee Yeon Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Immunogenic Cell Death ◽  
Cross Presentation

scholarly journals Immunogenic Cell Death-Based Cancer Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming-Zhu Jin ◽  
Xi-Peng Wang
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Adaptive Immunity ◽  
Cancer Vaccines ◽  
Antitumor Immunity ◽  
Immunogenic Cell Death ◽  
Cancer Vaccination ◽  
The Past ◽  
Molecular Patterns

Cancer immunotherapy has achieved great advancement in the past decades. Whereas, its response is largely limited in immunologically cold tumors, in an urgent need to be solve. In recent years, an increasing number of studies have shown that inducing immunogenic cell deaths (ICDs) is an attractive approach to activate antitumor immunity. Upon specific stress, cancer cells undergo ICDs and dying cancer cells release danger associated molecular patterns (DAMPs), produce neoantigens and trigger adaptive immunity. ICDs exert a cancer vaccine-like effect and Inducement of ICDs mimics process of cancer vaccination. In this review, we propose a concept of ICD-based cancer vaccines and summarize sources of ICD-based cancer vaccines and their challenges, which may broaden the understandings of ICD and cancer vaccines in cancer immunotherapy.

scholarly journals Laser nanobubbles induce immunogenic cell death in breast cancer

Nanoscale ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 3644-3653
Author(s):  
Hieu T. M. Nguyen ◽  
Nitesh Katta ◽  
Jessica A. Widman ◽  
Eri Takematsu ◽  
Xu Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Dendritic Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activation ◽  
Immunogenic Cell Death ◽  
Dendritic Cell Activation

Laser nanobubbles induce dendritic cell activation in breast cancer cells.

scholarly journals DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells

2021 ◽  
Vol 9 (5) ◽  
pp. e002054
Author(s):  
Francisco J Cueto ◽  
Carlos del Fresno ◽  
Paola Brandi ◽  
Alexis J. Combes ◽  
Elena Hernández-García ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Immunity ◽  
Elevated Serum ◽  
Dead Cell ◽  
Type I ◽  
Cross Presentation ◽  
Patients With Cancer ◽  
Deficient Mice

BackgroundConventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet.MethodsB16 and MC38 tumor cell lines were inoculated subcutaneously into wild-type (WT) and DNGR-1-deficient mice. To overexpress Flt3L systemically, we performed gene therapy through the hydrodynamic injection of an Flt3L-encoding plasmid. To characterize the immune response, we performed flow cytometry and RNA-Seq of tumor-infiltrating cDC1s.ResultsHere, we found that cross-presentation of tumor antigens in the steady state was DNGR-1-independent. However, on Flt3L systemic overexpression, tumor growth was delayed in DNGR-1-deficient mice compared with WT mice. Of note, this protection was recapitulated by anti-DNGR-1-blocking antibodies in mice following Flt3L gene therapy. This improved antitumor immunity was associated with Batf3-dependent enhanced accumulation of CD8+ T cells and cDC1s within tumors. Mechanistically, the deficiency in DNGR-1 boosted an Flt3L-induced specific inflammatory gene signature in cDC1s, including Ccl5 expression. Indeed, the increased infiltration of cDC1s within tumors and their protective effect rely on CCL5/CCR5 chemoattraction. Moreover, FLT3LG and CCL5 or CCR5 gene expression signatures correlate with an enhanced cDC1 signature and a favorable overall survival in patients with cancer. Notably, cyclophosphamide elevated serum Flt3L levels and, in combination with the absence of DNGR-1, synergized against tumor growth.ConclusionDNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression.

scholarly journals Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Miebach ◽  
Eric Freund ◽  
Stefan Horn ◽  
Felix Niessner ◽  
Sanjeev Kumar Sagwal ◽  
...  
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Treatment Time ◽  
Plasma Source ◽  
In Vivo Model ◽  
Antitumor Effects ◽  
Plasma Device

AbstractRecent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.

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.

Sign in / Sign up

Export Citation Format

Share Document