The DOI matches its Crossref record; 110 of the 110 references it cites were found in a registry or an index.
Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy
Open accessAbstract
Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell–infiltrated tumors. Significance: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors. This article is highlighted in the In This Issue feature, p. 1
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Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609 · cited 2×
“Patients with socalled cold or immune-desert tumors are, however, less likely to respond to ICB (1, 2).”
BackgroundPredictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231
Aran, D., Looney, A. P., Liu, L., Wu, E., Fong, V., Hsu, A., Chak, S., Naikawadi, R. P., Wolters, P. J., Abate, A. R., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0276-y · Cited by 4,984
Determining cell type abundance and expression from bulk tissues with digital cytometry
Newman, A. M., Steen, C. B., Liu, C. L., Gentles, A. J., Chaudhuri, A. A., Scherer, F., Khodadoust, M. S., Esfahani, M. S., Luca, B. A., Steiner, D., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0114-2 · Cited by 4,478
Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
Bindea, G., Mlecnik, B., Tosolini, M., Kirilovsky, A., Waldner, M., Obenauf, A. C., Angell, H., Fredriksen, T., Lafontaine, L., Berger, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.003 · Cited by 4,422
Calreticulin exposure dictates the immunogenicity of cancer cell death
Obeid, M., Tesniere, A., Ghiringhelli, F., Fimia, G. M., Apetoh, L., Perfettini, J.-L., Castedo, M., Mignot, G., Panaretakis, T., Casares, N., et al. (2007) · Nature Medicine · doi:10.1038/nm1523 · Cited by 3,216
Cited by
The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth
de Visser, K. E., & Joyce, J. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.016 · Cited by 4,059
Rahim, M. K., Okholm, T. L. H., Jones, K. B., McCarthy, E. E., Liu, C. C., Yee, J. L., Tamaki, S. J., Marquez, D. M., Tenvooren, I., Wai, K., et al. (2023) · Cell · doi:10.1016/j.cell.2023.02.021 · Cited by 455
Zhang, M., Liu, C., Tu, J., Tang, M., Ashrafizadeh, M., Nabavi, N., Sethi, G., Zhao, P., & Liu, S. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02305-x · Cited by 259
Shi, X., Wang, X., Yao, W., Shi, D., Shao, X., Lu, Z., Chai, Y., Song, J., Tang, W., & Wang, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01885-2 · Cited by 258
Metadata
- Authors
- Herrera, F. G., Ronet, C., Ochoa de Olza, M., Barras, D., Crespo, I., Andreatta, M., Corria-Osorio, J., Spill, A., Benedetti, F., Genolet, R., Orcurto, A., Imbimbo, M., Ghisoni, E., Navarro Rodrigo, B., Berthold, D. R., Sarivalasis, A., Zaman, K., Duran, R., Dromain, C., Prior, J., Schaefer, N., Bourhis, J., Dimopoulou, G., Tsourti, Z., Messemaker, M., Smith, T., Warren, S. E., Foukas, P., Rusakiewicz, S., Pittet, M. J., Zimmermann, S., Sempoux, C., Dafni, U., Harari, A., Kandalaft, L. E., Carmona, S. J., Dangaj Laniti, D., Irving, M., & Coukos, G.
- Venue
- Cancer Discovery
- Published
- 2021-09-03
- Volume
- 12
- Issue
- 1
- Pages
- 108-133
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W3197979465
- Cited by
- 451
- References
- 110
- FWCI
- 19.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Herrera, F. G., Ronet, C., Ochoa de Olza, M., Barras, D., Crespo, I., Andreatta, M., Corria-Osorio, J., Spill, A., Benedetti, F., Genolet, R., Orcurto, A., Imbimbo, M., Ghisoni, E., Navarro Rodrigo, B., Berthold, D. R., Sarivalasis, A., Zaman, K., Duran, R., Dromain, C., . . . Coukos, G. (2022). Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-21-0003
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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.
