Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect.

Abscopal effect anti-PD1 antibody irradiated-tumor volume radiation dose radiotherapy tumor-specific CD8+ T cells

Journal

American journal of cancer research
ISSN: 2156-6976
Titre abrégé: Am J Cancer Res
Pays: United States
ID NLM: 101549944

Informations de publication

Date de publication:
2020
Historique:
received: 30 03 2019
accepted: 26 12 2019
entrez: 21 3 2020
pubmed: 21 3 2020
medline: 21 3 2020
Statut: epublish

Résumé

Radiotherapy (RT) is the primary treatment for cancer. Ionizing radiation from RT induces tumor damage at the irradiated site, and, although clinically infrequent, may cause regression of tumors distant from the irradiated site-a phenomenon known as the abscopal effect. Recently, the abscopal effect has been related to prolongation of overall survival time in cancer patients, though the factors that influence the abscopal effect are not well understood. The aim of this study is to clarify the factors influencing on abscopal effect. Here, we established a mouse model in which we induced the abscopal effect. We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT.

Identifiants

pubmed: 32195019
pmc: PMC7061743

Types de publication

Journal Article

Langues

eng

Pagination

440-453

Informations de copyright

AJCR Copyright © 2020.

Déclaration de conflit d'intérêts

None.

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Auteurs

Kiichiro Baba (K)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Motoo Nomura (M)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Shinya Ohashi (S)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Takuya Hiratsuka (T)

Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Yukie Nakai (Y)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Tomoki Saito (T)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Yuki Kondo (Y)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Keita Fukuyama (K)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Osamu Kikuchi (O)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Atsushi Yamada (A)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Junichi Matsubara (J)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Kenshiro Hirohashi (K)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Yosuke Mitani (Y)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Ayaka Mizumoto (A)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Manabu Muto (M)

Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto 606-8507, Japan.

Classifications MeSH