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Cited by 202Immunotherapy and Immune ResponsesCell death mechanisms and regulationEndoplasmic Reticulum Stress and Disease

Ecto‐calreticulin in immunogenic chemotherapy

Obeid, Michel, Tesniere, Antoine, Panaretakis, Theocharis, Tufi, Roberta, Joza, Nick, Van Endert, Peter, Ghiringhelli, François, Apetoh, Lionel +6 more·2007·Immunological Reviews
DOI 10.1111/j.1600-065x.2007.00567.x
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Abstract

Summary:The conventional treatment of cancer relies upon radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Nonetheless, there are circumstances in which conventional anti‐cancer therapy can induce a modality of cellular demise that elicits innate and cognate immune responses, which in turn mediate part of the anti‐tumor effect. Although different chemotherapeutic agents may kill tumor cells through an apparently homogeneous apoptotic pathway, they differ in their capacity to stimulate immunogenic cell death. We discovered that the pre‐apoptotic translocation of intracellular calreticulin (endo‐CRT) to the plasma membrane surface (ecto‐CRT) is critical for the recognition and engulfment of dying tumor cells by dendritic cells. Thus, anthracyclines and γ‐irradiation that induce ecto‐CRT cause immunogenic cell death, while other pro‐apoptotic agents (such as mitomycin C and etoposide) induce neither ecto‐CRT nor immunogenic cell death. Depletion of CRT abolishes the immunogenicity of cell death elicited by anthracyclines, while exogenous supply of CRT or enforcement of CRT exposure by pharmacological agents that favor CRT translocation can enhance the immunogenicity of cell death. For optimal anti‐tumor vaccination and immunogenic chemotherapy, the same cells have to expose ecto‐CRT and to succumb to apoptosis; if these events affect different cells, no anti‐tumor immune response is elicited. These results may have far reaching implications for tumor immunology because (i) ecto‐CRT exposure by tumor cells allows for the prediction of therapeutic outcome and because (ii) the re‐establishment of ecto‐CRT may ameliorate the efficacy of chemotherapy.

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Crossref · 10.1111/j.1600-065x.2007.00567.x

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  • Potential immunogenic signals from dying cells include surface-exposed proteins such as calreticulin and heat shock proteins, lipid moieties such as phosphatidylserine that flip to the outer leaflet, released proteins such as HMGB1, and extracellular nucleic acids and their degradation products (oligonucleotides, nucleotides, nucleosides, urate).

    “Potential immunogenic signals emanating from dying cells include proteins that appear at the surface of stressed and dying cells (such as calreticulin and heat shock proteins, HSPs), lipid moieties that flip from the inner plasma membrane leaflet to the outer leaflet (such as phosphatidylserine) 38,60, proteins that are released into the supernatant of cells (such as HMGB1) 51, as well as nucleic”

    From Immunogenic and tolerogenic cell death (2009) · cites this paper as [38]

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Authors
Obeid, M., Tesniere, A., Panaretakis, T., Tufi, R., Joza, N., Van Endert, P., Ghiringhelli, F., Apetoh, L., Chaput, N., Flament, C., Ullrich, E., De Botton, S., Zitvogel, L., & Kroemer, G.
Affiliations
Université Paris-Sud (FR)
Corresponding author
Kroemer, Guido
ORCID
Venue
Immunological Reviews
Publisher
Wiley
Published
2007-10-30
Volume
220
Issue
1
Pages
22-34
ISSN
  • 0105-2896 (ISSN-L)
  • 1600-065X
DOI
10.1111/j.1600-065x.2007.00567.x
OpenAlex
W1984068314
Cited by
202
References
72
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 17 · 2020: 12 · 2019: 14 · 2018: 12 · 2017: 11 · 2016: 15 · 2015: 11 · 2014: 6 · 2013: 13 · 2012: 8
FWCI
1.20
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Immunological Reviews (publishedVersion)
  • PubMed (publishedVersion)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
immunogenic cell death, calreticulin, dendritic cells, anthracyclines, gamma irradiation, apoptosis, tumor immunology, cancer immunotherapy, mitomycin C, etoposide
MeSH terms
Animals, Cell Membrane, Humans, Neoplasms, Vaccination, Apoptosis, Anthracyclines, Protein Transport, Calreticulin, Mice

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