An Immunosurveillance Mechanism Controls Cancer Cell Ploidy
Open accessAbstract
Keeping Cancer Cells At Bay: Cancer cells are often aneuploid; that is, they have an abnormal number of chromosomes. But to what extent this contributes to the tumorigenic phenotype is not clear. Senovilla et al. (p. 1678 ; see the Perspective by Zanetti and Mahadevan ) found that tetraploidization of cancer cells can cause them to become immunogenic and thus aid in their clearance from the body by the immune system. Cells with excess chromosomes put stress on the endoplasmic reticulum, which leads to movement of the protein calreticulin to the cell surface. Calreticulin exposure in turn caused recognition of cancer cells in mice by the host immune system. Thus, the immune system appears to serve a protective role in eliminating hyperploid cells that must be overcome to allow unrestricted growth of cancer cells.
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Cells that cannot undergo mitotic exit show hallmarks of immunogenic cell death, where the immune system induces a strong response against the dying cells.
“Senovilla et al showed that cells that cannot undergo mitotic exit show hallmarks of immunogenic cell death where the immune system induces a strong response against the dying cells.31”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [31]
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Self-citation
- Authors
- Senovilla, L., Vitale, I., Martins, I., Tailler, M., Pailleret, C., Michaud, M., Galluzzi, L., Adjemian, S., Kepp, O., Niso-Santano, M., Shen, S., Mariño, G., Criollo, A., Boilève, A., Job, B., Ladoire, S., Ghiringhelli, F., Sistigu, A., Yamazaki, T., Rello-Varona, S., Locher, C., Poirier-Colame, V., Talbot, M., Valent, A., Berardinelli, F., Antoccia, A., Ciccosanti, F., Fimia, G. M., Piacentini, M., Fueyo, A., Messina, N. L., Li, M., Chan, C. J., Sigl, V., Pourcher, G., Ruckenstuhl, C., Carmona-Gutierrez, D., Lazar, V., Penninger, J. M., Madeo, F., López-Otín, C., Smyth, M. J., Zitvogel, L., Castedo, M., & Kroemer, G.
- Affiliations
- Université Paris-Sud (FR)
- INSERM, U848, Villejuif, France.
- Institut Gustave Roussy (FR)
- Inserm (FR)
- Pathologie Moléculaire, Departement De Biologie et Pathologie Médicales, Villejuif, France.
- Roma Tre University (IT)
- Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT)
- National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
- University of Rome Tor Vergata (IT)
- Universidad de Oviedo (ES)
- The University of Melbourne (AU)
- Peter MacCallum Cancer Centre (AU)
- Institute of Molecular Biotechnology (AT)
- Institute for Molecular Bioscience, Graz, Austria.
- Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, IUOPA, Universidad de Oviedo, Oviedo, Spain.
- Corresponding author
- Zitvogel, Laurence
- Castedo, Maria
- Kroemer, Guido
- ORCID
- Senovilla, Laura
- Vitale, Ilio
- Martins, Isabelle
- Pailleret, Claire
- Galluzzi, Lorenzo
- Adjemian, Sandy
- Kepp, Oliver
- Shen, Shensi
- Mariño, Guillermo
- Criollo, Alfredo
- Boilève, Alice
- Job, Bastien
- Ladoire, Sylvain
- Ghiringhelli, François
- Sistigu, Antonella
- Yamazaki, Takahiro
- Locher, Clara
- Berardinelli, Francesco
- Ciccosanti, Fabiola
- Piacentini, Mauro
- Fueyo, Antonio
- Messina, Nicole L.
- Li, Ming
- Chan, Christopher J.
- Sigl, Verena
- Pourcher, Guillaume
- Ruckenstuhl, Christoph
- Lazar, Vladimir
- Penninger, Josef M.
- Madeo, Frank
- Smyth, Mark J.
- Zitvogel, Laurence
- Castedo, Maria
- Kroemer, Guido
- Venue
- Science
- Published
- 2012-09-28
- Volume
- 337
- Issue
- 6102
- Pages
- 1678-1684
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2085234652
- Cited by
- 436
- References
- 50
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 30 · 2023: 38 · 2022: 23 · 2021: 34 · 2020: 28 · 2019: 31 · 2018: 41 · 2017: 30 · 2016: 32 · 2015: 47 · 2014: 32 · 2013: 38 · 2012: 6
- FWCI
- 19.47
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Institutional Repository University of Extremadura (University of Extremadura) (submittedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Iris (Roma Tre University) (submittedVersion)
- AIRUS (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- tumor surveillance, hyperploidy, tetraploidization, calreticulin exposure, endoplasmic reticulum stress response, immunogenicity, tumor immunogenicity, DNA content, immunoselection, carcinogenesis
- MeSH terms
- Animals, DNA, Neoplasm, Humans, Immunocompetence, Immunologic Surveillance, Mice, Inbred BALB C, Neoplasms, Phosphorylation, Ploidies, Eukaryotic Initiation Factor-2, Common Variable Immunodeficiency, Calreticulin, Cell Line, Tumor, Mice, Endoplasmic Reticulum Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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