Immunogenic Cell Death in Cancer Therapy
Abstract
Depending on the initiating stimulus, cancer cell death can be immunogenic or nonimmunogenic. Immunogenic cell death (ICD) involves changes in the composition of the cell surface as well as the release of soluble mediators, occurring in a defined temporal sequence. Such signals operate on a series of receptors expressed by dendritic cells to stimulate the presentation of tumor antigens to T cells. We postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies. Hence, suboptimal regimens (failing to induce ICD), selective alterations in cancer cells (preventing the emission of immunogenic signals during ICD), or defects in immune effectors (abolishing the perception of ICD by the immune system) can all contribute to therapeutic failure. We surmise that ICD and its subversion by pathogens also play major roles in antiviral immune responses.
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CRT translocation from endoplasmic reticulum to the out-layer of plasma membrane depends on ER stress and is associated with PERK-mediated eIF2α phosphorylation.
“It is known that CRT translocation from endoplasmic reticulum (ER) to the out-layer of plasma membrane depends on an ER stress and associated with ER kinase (PERK)-mediated eIF2α phosphorylation [18, 19].”
From Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma (2015) · cites this paper as [18]
ICD can be initiated by viral infection, some FDA-approved chemotherapeutics (e.g., anthracyclines, bortezomib), specific forms of radiation therapy, and hypericin-based photodynamic therapy.
“ICD can be initiated by a relatively restricted set of stimuli, including viral infection, some FDA-approved chemotherapeutics (e.g., anthracyclines, bortezomib), specific forms of radiation therapy, and hypericin-based photodynamic therapy [854–861].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [858]
The ATP-P2RX7 signaling recruits DCs into the tumor bed; the CRT-CD91 axis promotes DC to engulf cancer antigens; the HMGB1-TLR4 pathway facilitates optimal cancer antigen presentation.
“The ATP-P2RX7 signaling recruits DCs into the tumor bed; the CRT-CD91 axis promotes DC to engulf cancer antigens; the HMGB1-TLR4 pathway facilitates the optimal cancer antigen presentation [36].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [36]
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- Authors
- Kroemer, G., Galluzzi, L., Kepp, O., & Zitvogel, L.
- Affiliations
- Sorbonne Paris Cité (FR)
- Institut Gustave Roussy (FR)
- Université Paris-Sud (FR)
- Corresponding author
- Galluzzi, Lorenzo
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2013-03-21
- Volume
- 31
- Issue
- 1
- Pages
- 51-72
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2120426523
- Cited by
- 3,303
- References
- 112
- Citations by year
- 2026: 207 · 2025: 266 · 2024: 288 · 2023: 373 · 2022: 365 · 2021: 339 · 2020: 308 · 2019: 206 · 2018: 182 · 2017: 176 · 2016: 198 · 2015: 175 · 2014: 139 · 2013: 76 · 2012: 2
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- Ligue Contre le Cancer
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- immunogenic cell death, cancer immunotherapy, dendritic cells, tumor antigen presentation, T cell activation, soluble mediators, cell surface changes, immune evasion, treatment failure, antiviral immunity
- MeSH terms
- Animals, Humans, Immunity, Cellular, Neoplasms, Cell Death, Cancer Vaccines
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