The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11
Open accessAbstract
A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy. Significance: This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy. This article is highlighted in the In This Issue feature, p. 1631
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Cites
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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
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Self-citationACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088
CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
Wang, W., Green, M., Choi, J. E., Gijón, M., Kennedy, P. D., Johnson, J. K., Liao, P., Lang, X., Kryczek, I., Sell, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1170-y · Cited by 2,880
Self-citationRadiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Twyman-Saint Victor, C., Rech, A. J., Maity, A., Rengan, R., Pauken, K. E., Stelekati, E., Benci, J. L., Xu, B., Dada, H., Odorizzi, P. M., et al. (2015) · Nature · doi:10.1038/nature14292 · Cited by 2,434
Cited by
Targeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099
Ferroptosis: Mechanisms and links with diseases
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00428-9 · Cited by 1,471
The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression
Lei, G., Zhang, Y., Koppula, P., Liu, X., Zhang, J., Lin, S. H., Ajani, J. A., Xiao, Q., Liao, Z., Wang, H., et al. (2020) · Cell Research · doi:10.1038/s41422-019-0263-3 · Cited by 1,318
CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4
Liao, P., Wang, W., Wang, W., Kryczek, I., Li, X., Bian, Y., Sell, A., Wei, S., Grove, S., Johnson, J. K., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.02.003 · Cited by 912
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Metadata
- Authors
- Lang, X., Green, M. D., Wang, W., Yu, J., Choi, J. E., Jiang, L., Liao, P., Zhou, J., Zhang, Q., Dow, A., Saripalli, A. L., Kryczek, I., Wei, S., Szeliga, W., Vatan, L., Stone, E. M., Georgiou, G., Cieslik, M., Wahl, D. R., Morgan, M. A., Chinnaiyan, A. M., Lawrence, T. S., & Zou, W.
- Venue
- Cancer Discovery
- Published
- 2019-12-01
- Volume
- 9
- Issue
- 12
- Pages
- 1673-1685
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2975105312
- Cited by
- 1,047
- References
- 43
- FWCI
- 63.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Lang, X., Green, M. D., Wang, W., Yu, J., Choi, J. E., Jiang, L., Liao, P., Zhou, J., Zhang, Q., Dow, A., Saripalli, A. L., Kryczek, I., Wei, S., Szeliga, W., Vatan, L., Stone, E. M., Georgiou, G., Cieslik, M., Wahl, D. R., . . . Zou, W. (2019). Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-19-0338
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
