干旱区生态环境知识资源中心(Arid): Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

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DOI	10.1158/2159-8290.CD-21-0003
	Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy
	Herrera, Fernanda G.; Ronet, Catherine; de Olza, Maria Ochoa; Barras, David; Crespo, Isaac; Andreatta, Massimo; Corria-Osorio, Jesus; Spill, Aodrenn; Benedetti, Fabrizio; Genolet, Raphael; Orcurto, Angela; Imbimbo, Martina; Ghisoni, Eleonora; Rodrigo, Blanca Navarro; Berthold, Dominik R.; Sarivalasis, Apostolos; Zaman, Khalil; Duran, Rafael; Dromain, Clarisse; Prior, John; Schaefer, Niklaus; Bourhis, Jean; Dimopoulou, Georgia; Tsourti, Zoi; Messemaker, Marius; Smith, Thomas; Warren, Sarah E.; Foukas, Periklis; Rusakiewicz, Sylvie; Pittet, Mikael J.; Zimmermann, Stefan; Sempoux, Christine; Dafni, Urania; Harari, Alexandre; Kandalaft, Lana E.; Carmona, Santiago J.; Laniti, Denarda Dangaj; Irving, Melita; Coukos, George
通讯作者	Coukos, G (corresponding author)，Lausanne Univ Hosp, Dept Oncol, Rue Bugnon 46, BH-09701 Lausanne, Switzerland.
来源期刊	CANCER DISCOVERY
ISSN	2159-8274
EISSN	2159-8290
出版年	2022
卷号	12 期号:1
英文摘要	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.
类型	Article
语种	英语
开放获取类型	Green Published, hybrid
收录类别	SCI-E
WOS记录号	WOS:000745655900001
WOS关键词	CD4(+) T-CELLS ; CHECKPOINT BLOCKADE ; ANTITUMOR IMMUNITY ; RADIATION-THERAPY ; CTLA-4 BLOCKADE ; LOCAL RADIATION ; PD-1 BLOCKADE ; CUTTING EDGE ; MIC LIGANDS ; MOUSE MODEL
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/376794
作者单位	[Herrera, Fernanda G.; Ronet, Catherine; de Olza, Maria Ochoa; Barras, David; Crespo, Isaac; Andreatta, Massimo; Corria-Osorio, Jesus; Spill, Aodrenn; Benedetti, Fabrizio; Genolet, Raphael; Rusakiewicz, Sylvie; Harari, Alexandre; Kandalaft, Lana E.; Carmona, Santiago J.; Laniti, Denarda Dangaj; Irving, Melita; Coukos, George] Univ Lausanne, Lausanne Branch, Ludwig Inst Canc Res, Lausanne, Switzerland; [Herrera, Fernanda G.; Bourhis, Jean] Lausanne Univ Hosp, Dept Oncol, Radiat Oncol Serv, Lausanne, Switzerland; [Herrera, Fernanda G.; de Olza, Maria Ochoa; Orcurto, Angela; Imbimbo, Martina; Ghisoni, Eleonora; Rodrigo, Blanca Navarro; Zimmermann, Stefan; Coukos, George] Lausanne Univ Hosp, Dept Oncol, Immunooncol Serv, Lausanne, Switzerland; [Berthold, Dominik R.; Sarivalasis, Apostolos; Zaman, Khalil] Lausanne Univ Hosp, Dept Oncol, Med Oncol Serv, Lausanne, Switzerland; [Duran, Rafael; Dromain, Clarisse] Lausanne Univ Hosp, Dept Radiol & Intervent Radiol, Lausanne, Switzerland; [Prior, John; Schaefer, Nik...
推荐引用方式 GB/T 7714	Herrera, Fernanda G.,Ronet, Catherine,de Olza, Maria Ochoa,et al. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy[J],2022,12(1).
APA	Herrera, Fernanda G..,Ronet, Catherine.,de Olza, Maria Ochoa.,Barras, David.,Crespo, Isaac.,...&Coukos, George.(2022).Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.CANCER DISCOVERY,12(1).
MLA	Herrera, Fernanda G.,et al."Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy".CANCER DISCOVERY 12.1(2022).