Immunogenic cell stress and death
Abstract
Dying mammalian cells emit numerous signals that interact with the host to dictate the immunological correlates of cellular stress and death. In the absence of reactive antigenic determinants (which is generally the case for healthy cells), such signals may drive inflammation but cannot engage adaptive immunity. Conversely, when cells exhibit sufficient antigenicity, as in the case of infected or malignant cells, their death can culminate with adaptive immune responses that are executed by cytotoxic T lymphocytes and elicit immunological memory. Suggesting a key role for immunogenic cell death (ICD) in immunosurveillance, both pathogens and cancer cells evolved strategies to prevent the recognition of cell death as immunogenic. Intriguingly, normal cells succumbing to conditions that promote the formation of post-translational neoantigens (for example, oxidative stress) can also drive at least some degree of antigen-specific immunity, pointing to a novel implication of ICD in the etiology of non-infectious, non-malignant disorders linked to autoreactivity.
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The combination of genotoxic chemotherapy and radiotherapy with immunotherapy is based on the rationale that cytotoxic treatment results in genomic instability and cell death, thereby stimulating both production of neo-antigens and eliciting an adaptive immune response that can be further unleashed by immune checkpoint blockade.
“The combination of genotoxic chemotherapy and radiotherapy with immunotherapy is a third approach to foster immune activation in pMMR/MSS CRC and is based on the rationale that cytotoxic treatment would result in genomic instability and cell death, thereby stimulating both the production of neo-antigens and eliciting an adaptive immune response that can be further unleashed by ICB.138”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [138]
Stimulation of autophagy improves the therapeutic outcome of immunogenic chemotherapy in mice.
“Moreover, stimulation of autophagy improves the therapeutic outcome of immunogenic chemotherapy in mice.162”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [162]
Cites
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationGut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671 · see citing works
Self-citationGut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812 · see citing works
Self-citationNeoantigens in cancer immunotherapy
Schumacher, T. N., & Schreiber, R. D. (2015) · Science · doi:10.1126/science.aaa4971 · Cited by 4,783 · see citing works
Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., Mignot, G., Maiuri, M. C., Ullrich, E., Saulnier, P., et al. (2007) · Nature Medicine · doi:10.1038/nm1622 · Cited by 3,056 · see citing works
Self-citationRegulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins
Singh, R., Letai, A., & Sarosiek, K. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0089-8 · Cited by 2,111 · see citing works
Hildner, K., Edelson, B. T., Purtha, W. E., Diamond, M., Matsushita, H., Kohyama, M., Calderon, B., Schraml, B. U., Unanue, E. R., Diamond, M. S., et al. (2008) · Science · doi:10.1126/science.1164206 · Cited by 2,081 · see citing works
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052 · see citing works
Tertiary lymphoid structures in the era of cancer immunotherapy
Sautès-Fridman, C., Petitprez, F., Calderaro, J., & Fridman, W. H. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0144-6 · Cited by 1,884 · see citing works
Majeti, R., Chao, M. P., Alizadeh, A. A., Pang, W. W., Jaiswal, S., Gibbs, K. D., van Rooijen, N., & Weissman, I. L. (2009) · Cell · doi:10.1016/j.cell.2009.05.045 · Cited by 1,752 · see citing works
Type I interferons in anticancer immunity
Zitvogel, L., Galluzzi, L., Kepp, O., Smyth, M. J., & Kroemer, G. (2015) · Nature Reviews Immunology · doi:10.1038/nri3845 · Cited by 1,305 · see citing works
Self-citationLauber, K., Bohn, E., Kröber, S. M., Xiao, Y.-J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00422-7 · Cited by 967 · see citing works
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925 · see citing works
Mechanisms of pre‐apoptotic calreticulin exposure in immunogenic cell death
Panaretakis, T., Kepp, O., Brockmeier, U., Tesniere, A., Bjorklund, A., Chapman, D. C., Durchschlag, M., Joza, N., Pierron, G., van Endert, P., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.1 · Cited by 848 · see citing works
Self-citationA novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death
Garg, A. D., Krysko, D. V., Verfaillie, T., Kaczmarek, A., Ferreira, G. B., Marysael, T., Rubio, N., Firczuk, M., Mathieu, C., Roebroek, A. J. M., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2011.497 · Cited by 800 · see citing works
Caloric restriction mimetics enhance anticancer immunosurveillance
Pietrocola, F., Pol, J., Vacchelli, E., Rao, S., Enot, D. P., Baracco, E. E., Levesque, S., Castoldi, F., Jacquelot, N., Yamazaki, T., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.016 · Cited by 542 · see citing works
Regulated cell death and inflammation: an auto-amplification loop causes organ failure
Linkermann, A., Stockwell, B. R., Krautwald, S., & Anders, H.-J. (2014) · Nature Reviews Immunology · doi:10.1038/nri3743 · Cited by 522 · see citing works
López-Otín, C., & Kroemer, G. (2021) · Cell · doi:10.1016/j.cell.2020.11.034 · Cited by 499 · see citing works
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Wolf, A. J., & Underhill, D. M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.136 · Cited by 469 · see citing works
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1
Vacchelli, E., Ma, Y., Baracco, E. E., Sistigu, A., Enot, D. P., Pietrocola, F., Yang, H., Adjemian, S., Chaba, K., Semeraro, M., et al. (2015) · Science · doi:10.1126/science.aad0779 · Cited by 452 · see citing works
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Rodriguez-Ruiz, M. E., Vitale, I., Harrington, K. J., Melero, I., & Galluzzi, L. (2020) · Nature Immunology · doi:10.1038/s41590-019-0561-4 · Cited by 385 · see citing works
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Yamazaki, T., Kirchmair, A., Sato, A., Buqué, A., Rybstein, M., Petroni, G., Bloy, N., Finotello, F., Stafford, L., Navarro Manzano, E., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0751-0 · Cited by 359 · see citing works
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Garg, A. D., Dudek, A. M., Ferreira, G. B., Verfaillie, T., Vandenabeele, P., Krysko, D. V., Mathieu, C., & Agostinis, P. (2013) · Autophagy · doi:10.4161/auto.25399 · Cited by 305 · see citing works
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Liu, P., Zhao, L., Pol, J., Levesque, S., Petrazzuolo, A., Pfirschke, C., Engblom, C., Rickelt, S., Yamazaki, T., Iribarren, K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09415-3 · Cited by 302 · see citing works
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Petroni, G., Formenti, S. C., Chen-Kiang, S., & Galluzzi, L. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0300-y · Cited by 163 · see citing works
Self-citationRodriguez-Ruiz, M. E., Buqué, A., Hensler, M., Chen, J., Bloy, N., Petroni, G., Sato, A., Yamazaki, T., Fucikova, J., & Galluzzi, L. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1655964 · Cited by 147 · see citing works
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Buqué, A., Bloy, N., Perez-Lanzón, M., Iribarren, K., Humeau, J., Pol, J. G., Levesque, S., Mondragon, L., Yamazaki, T., Sato, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17644-0 · Cited by 138 · see citing works
Self-citationLadoire, S., Enot, D., Senovilla, L., Ghiringhelli, F., Poirier-Colame, V., Chaba, K., Semeraro, M., Chaix, M., Penault-Llorca, F., Arnould, L., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1154244 · Cited by 117 · see citing works
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- Authors
- Kroemer, G., Galassi, C., Zitvogel, L., & Galluzzi, L.
- Affiliations
- Inserm (FR)
- Weill Cornell Medicine (US)
- Corresponding author
- Kroemer, Guido
- Galluzzi, Lorenzo
- Venue
- Nature Immunology
- Published
- 2022-02-10
- Volume
- 23
- Issue
- 4
- Pages
- 487-500
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W4211133027
- Semantic Scholar
- e9c51580a6f717006c331ac1fbd7d42c395ae026
- Cited by
- 1,353
- References
- 32
- Citations by year
- 2026: 230 · 2025: 402 · 2024: 353 · 2023: 269 · 2022: 99
- FWCI
- 29.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-18-IDEX-0001)
- 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, neoantigens, oxidative stress, cytotoxic T lymphocytes, immunological memory, tumor surveillance, autoreactivity, inflammation, adaptive immunity
- MeSH terms
- Immunogenic Cell Death, Animals, Antigens, Mammals, Neoplasms, Cell Death, Adaptive Immunity
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