The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling
Open accessAbstract
Clinical oncology heavily relies on the use of radiotherapy, which often leads to merely transient responses that are followed by local or distant relapse. The molecular mechanisms explaining radioresistance are largely elusive. Here, we identified a dual role of autophagy in the response of cancer cells to ionizing radiation. On one hand, we observed that the depletion of essential autophagy-relevant gene products, such as ATG5 and Beclin 1, increased the sensitivity of human or mouse cancer cell lines to irradiation, both in vitro (where autophagy inhibition increased radiation-induced cell death and decreased clonogenic survival) and in vivo, after transplantation of the cell lines into immunodeficient mice (where autophagy inhibition potentiated the tumour growth-inhibitory effect of radiotherapy). On the other hand, when tumour proficient or deficient for autophagy were implanted in immunocompetent mice, it turned out that defective autophagy reduced the efficacy of radiotherapy. Indeed, radiotherapy elicited an anti-cancer immune response that was dependent on autophagy-induced ATP release from stressed or dying tumour cells and was characterized by dense lymphocyte infiltration of the tumour bed. Intratumoural injection of an ecto-ATPase inhibitor restored the immune infiltration of autophagy-deficient tumours post radiotherapy and improved the growth-inhibitory effect of ionizing irradiation. Altogether, our results reveal that beyond its cytoprotective function, autophagy confers immunogenic properties to tumours, hence amplifying the efficacy of radiotherapy in an immunocompetent context. This has far-reaching implications for the development of pharmacological radiosensitizers.
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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
Self-citationGalluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421
Self-citationPromotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311
Rabinowitz, J. D., & White, E. (2010) · Science · doi:10.1126/science.1193497 · Cited by 1,982
Immunological aspects of cancer chemotherapy
Zitvogel, L., Apetoh, L., Ghiringhelli, F., & Kroemer, G. (2008) · Nature Reviews Immunology · doi:10.1038/nri2216 · Cited by 1,712
Self-citationMolecular dissection of autophagy: two ubiquitin-like systems
Ohsumi, Y. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056522 · Cited by 1,240 · cited 1×
“is based on subsequent protein conjugation steps.(10) The initial formation of ATG5–ATG12 complexes allows for the recruitment of ATG8 (LC3 in mammalian cells) by phospha-”
BackgroundObeid, M., Panaretakis, T., Joza, N., Tufi, R., Tesniere, A., van Endert, P., Zitvogel, L., & Kroemer, G. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402201 · Cited by 474
Self-citationEcto‐calreticulin in immunogenic chemotherapy
Obeid, M., Tesniere, A., Panaretakis, T., Tufi, R., Joza, N., Van Endert, P., Ghiringhelli, F., Apetoh, L., Chaput, N., Flament, C., et al. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00567.x · Cited by 202 · cited 1×
“exposed at the cell surface or are released into the extracellular space, thus stimulating anti-tumour immune responses.(23,24) Adenosine triphosphate (ATP) is one of the danger signals released during ICD.”
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Cited by
Immunogenic cell death in cancer and infectious disease
Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.107 · Cited by 3,119
Self-citationLevy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526
Self-consumption: the interplay of autophagy and apoptosis
Mariño, G., Niso-Santano, M., Baehrecke, E. H., & Kroemer, G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3735 · Cited by 2,172
Self-citationAutophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Self-citationAutophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182
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Metadata
- Authors
- Ko, A., Kanehisa, A., Martins, I., Senovilla, L., Chargari, C., Dugue, D., Mariño, G., Kepp, O., Michaud, M., Perfettini, J.-L., Kroemer, G., & Deutsch, E.
- Venue
- Cell Death & Differentiation
- Published
- 2013-09-13
- Volume
- 21
- Issue
- 1
- Pages
- 92-99
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W2077556440
- Cited by
- 205
- References
- 8
- FWCI
- 15.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ko, A., Kanehisa, A., Martins, I., Senovilla, L., Chargari, C., Dugue, D., Mariño, G., Kepp, O., Michaud, M., Perfettini, J.-L., Kroemer, G., & Deutsch, E. (2014). Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling. Cell Death & Differentiation. https://doi.org/10.1038/cdd.2013.124
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