scholarly journals Novel calreticulin-nanoparticle in combination with focused ultrasound induces immunogenic cell death in melanoma to enhance antitumor immunity

Theranostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 3397-3412 ◽  
Author(s):  
Sri Nandhini Sethuraman ◽  
Mohit Pratap Singh ◽  
Girish Patil ◽  
Shitao Li ◽  
Steven Fiering ◽  
...  
Keyword(s):  
Cell Death ◽  
Antitumor Immunity ◽  
Focused Ultrasound ◽  
Immunogenic Cell Death

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.

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.

scholarly journals The Concept of Immunogenic Cell Death in Antitumor Immunity

2015 ◽  
Vol 28 (Suppl 4) ◽  
pp. 4S48-4S55 ◽  
Author(s):  
Jitka Fučíková ◽  
Jiřina Bartůňková ◽  
Radek Špíšek
Keyword(s):  
Cell Death ◽  
Antitumor Immunity ◽  
Immunogenic Cell Death

Abstract B151: Exploring the induction of immunogenic cell death (ICD) by high-intensity focused ultrasound (HIFU)

2019 ◽  
Author(s):  
Heleen Dewitte ◽  
Yanou Engelen ◽  
Guillaume Lajoinie ◽  
Lígia Gomes-da-Silva ◽  
Michel Versluis ◽  
...  
Keyword(s):  
Cell Death ◽  
High Intensity ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Immunogenic Cell Death

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 Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4756
Author(s):  
Ryungsa Kim ◽  
Takanori Kin
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Tumor Cells ◽  
Anticancer Agents ◽  
Immune Activation ◽  
Primary Breast Cancer ◽  
Antitumor Immunity ◽  
Residual Tumor ◽  
Immunogenic Cell Death

How primary breast cancer can be cured after (neo)adjuvant therapy remains unclear at the molecular level. Immune activation by anticancer agents may contribute to residual tumor cell eradication with postsurgical (neo)adjuvant chemotherapy. Chemotherapy-induced immunogenic cell death (ICD) may result in long-term immune activation with memory effector T cells, leading to a primary breast cancer cure. Anthracycline and taxane treatments cause ICD and immunogenic modulations, resulting in the activation of antitumor immunity through damage-associated molecular patterns (DAMPs), such as adenosine triphosphate, calreticulin, high mobility group box 1, heat shock proteins 70/90, and annexin A1. This response may eradicate residual tumor cells after surgical treatment. Although DAMP release is also implicated in tumor progression, metastasis, and drug resistance, thereby representing a double-edged sword, robust immune activation by anticancer agents and the subsequent acquisition of long-term antitumor immune memory can be essential components of the primary breast cancer cure. This review discusses the molecular mechanisms by which anticancer drugs induce ICD and immunogenic modifications for antitumor immunity and targeted anti-DAMP therapy. Our aim was to improve the understanding of how to eradicate residual tumor cells treated with anticancer drugs and cure primary breast cancer by enhancing antitumor immunity with immune checkpoint inhibitors and vaccines.

MnO x Nanospikes as Nanoadjuvants and Immunogenic Cell Death Drugs with Enhanced Antitumor Immunity and Antimetastatic Effect

2020 ◽  
Vol 59 (38) ◽  
pp. 16381-16384 ◽  
Author(s):  
Binbin Ding ◽  
Pan Zheng ◽  
Fan Jiang ◽  
Yajie Zhao ◽  
Meifang Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Antitumor Immunity ◽  
Immunogenic Cell Death ◽  
Antimetastatic Effect
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