Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_D82928F3BB2B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.
Journal
Cancer discovery
Author(s)
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.
ISSN
2159-8290 (Electronic)
ISSN-L
2159-8274
Publication state
Published
Issued date
01/2022
Peer-reviewed
Oui
Volume
12
Number
1
Pages
108-133
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 <sup>+</sup> and CD8 <sup>+</sup> T cells. LDRT elicited predominantly CD4 <sup>+</sup> 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 <sup>+</sup> 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 <sup>+</sup> 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.
Pubmed
Web of science
Open Access
Yes
Create date
06/09/2021 7:16
Last modification date
21/11/2022 8:22
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