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Cited by 201Immunotherapy and Immune ResponsesCancer Immunotherapy and BiomarkersCell death mechanisms and regulation

The DOI matches its Crossref record; 126 of the 127 references it cites were found in a registry or an index.

Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

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Adkins, Irena, Fucikova, Jitka, Garg, Abhishek D, Agostinis, Patrizia, Špíšek, Radek·2014·OncoImmunology
DOI 10.4161/21624011.2014.968434PMC PMC4352954
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Abstract

The concept of immunogenic cancer cell death (ICD), as originally observed during the treatment with several chemotherapeutics or ionizing irradiation, has revolutionized the view on the development of new anticancer therapies. ICD is defined by endoplasmic reticulum (ER) stress response, reactive oxygen species (ROS) generation, emission of danger-associated molecular patterns and induction of antitumor immunity. Here we describe known and emerging cancer cell death-inducing physical modalities, such as ionizing irradiation, ultraviolet C light, Photodynamic Therapy (PDT) with Hypericin, high hydrostatic pressure (HHP) and hyperthermia (HT), which have been shown to elicit effective antitumor immunity. We discuss the evidence of ICD induced by these modalities in cancer patients together with their applicability in immunotherapeutic protocols and anticancer vaccine development.

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Crossref · 10.4161/21624011.2014.968434

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Figures

Figure 1. Timeline of the most important discoveries in the field of immunogenic cell death. Abbreviations: ATP, Adenosine triphosphate; CRT, calreticulin; DC, dendritic cell; HMGB1, high mobility group box 1; HSP90, heat shock protein 90; Hyp-PDT, photodynamic therapy with hypericin; ICD, immunogenic cell death; LRP, lipoprotein receptor-related proteins; MyD88, myeloid differentiation primary response gene 88; TLR, toll like receptor; UVC, ultraviolet light C.
Figure 1. Timeline of the most important discoveries in the field of immunogenic cell death. Abbreviations: ATP, Adenosine triphosphate; CRT, calreticulin; DC, dendritic cell; HMGB1, high mobility group box 1; HSP90, heat shock protein 90; Hyp-PDT, photodynamic therapy with hypericin; ICD, immunogenic cell death; LRP, lipoprotein receptor-related proteins; MyD88, myeloid differentiation primary response gene 88; TLR, toll like receptor; UVC, ultraviolet light C.CC BY · PubMed Central
Figure 2. A schematic representation of DC-based vaccine preparation using immunogenic HHP-killed tumor cells. Tumor cells treated with HHP (or other physical ICD-inducing modalities) expose various danger signals, so called DAMPs, in different stages of apoptosis. These DAMPs include calreticulin (CRT), heat shock proteins 70/90 (HSP70/90), HMGB1 and ATP. These molecules bind to respective cognate receptors like CD91 (for CRT/HSPs), TLR2/TLR4 (for HMGB1 or HSP70), P2RX7/P2RY2 (for ATP), respectively, on the cell surface of DCs. This leads to an enhanced engulfment of tumor cells and DC maturation characterized by upregulation of costimulatory molecules such as CD80, CD83, CD86 and HLA-DR, and by a distinct pro-inflammatory cytokine pattern. Activated DCs efficiently present tumor-specific antigens in the context of MHC class I and II molecules to T cells, inducing antitumor CD4+ and CD8+ T cell responses. Abbreviations: ATP, Adenosine triphosphate; CRT, calreticulin; CTL, cytotoxic T lymphocytes; DAMPs, danger-associated molecular patterns; DC, dendritic cell; HHP, high hydrostatic pressure; HMGB1, high mobility group box 1 HSP70, heat shock protein 70; HSP90, heat shock protein 90; ICD, immunogenic cell death; P2RX7, P2X purinoceptor 7; P2RY2, P2Y purinoceptor 2; RAGE, receptor for advanced glycation endproducts; TLR, toll like receptor.
Figure 2. A schematic representation of DC-based vaccine preparation using immunogenic HHP-killed tumor cells. Tumor cells treated with HHP (or other physical ICD-inducing modalities) expose various danger signals, so called DAMPs, in different stages of apoptosis. These DAMPs include calreticulin (CRT), heat shock proteins 70/90 (HSP70/90), HMGB1 and ATP. These molecules bind to respective cognate receptors like CD91 (for CRT/HSPs), TLR2/TLR4 (for HMGB1 or HSP70), P2RX7/P2RY2 (for ATP), respectively, on the cell surface of DCs. This leads to an enhanced engulfment of tumor cells and DC maturation characterized by upregulation of costimulatory molecules such as CD80, CD83, CD86 and HLA-DR, and by a distinct pro-inflammatory cytokine pattern. Activated DCs efficiently present tumor-specific antigens in the context of MHC class I and II molecules to T cells, inducing antitumor CD4+ and CD8+ T cell responses. Abbreviations: ATP, Adenosine triphosphate; CRT, calreticulin; CTL, cytotoxic T lymphocytes; DAMPs, danger-associated molecular patterns; DC, dendritic cell; HHP, high hydrostatic pressure; HMGB1, high mobility group box 1 HSP70, heat shock protein 70; HSP90, heat shock protein 90; ICD, immunogenic cell death; P2RX7, P2X purinoceptor 7; P2RY2, P2Y purinoceptor 2; RAGE, receptor for advanced glycation endproducts; TLR, toll like receptor.CC BY · PubMed Central

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Research works printed but not linked: 10

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Metadata

Authors
Adkins, I., Fucikova, J., Garg, A. D., Agostinis, P., & Špíšek, R.
Affiliations
  • Charles University (CZ)
  • KU Leuven (BE)
Corresponding author
  • Adkins, Irena
  • Špíšek, Radek
ORCID
Venue
OncoImmunology
Publisher
Informa UK Limited
Published
2014-11-03
Volume
3
Issue
12
Pages
e968434
ISSN
  • 2162-4011 (ISSN-L)
  • 2162-402X
DOI
10.4161/21624011.2014.968434
PMC
PMC4352954
OpenAlex
W2081035306
Cited by
200
References
127
Citations by year
2026: 8 · 2025: 16 · 2024: 12 · 2023: 20 · 2022: 17 · 2021: 19 · 2020: 24 · 2019: 17 · 2018: 15 · 2017: 18 · 2016: 22 · 2015: 11
FWCI
1.66
Type
journal article
Language
en
Open access
Licence
Locations
  • OncoImmunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
immunogenic cancer cell death, physical agents, ionizing irradiation, ultraviolet C light, photodynamic therapy, hypericin, high hydrostatic pressure, hyperthermia, endoplasmic reticulum stress, reactive oxygen species, damage-associated molecular patterns, antitumor immunity, cancer immunotherapy, cancer vaccines

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