Postablation Modulation after Single High-Dose Radiation Therapy Improves Tumor Control via Enhanced Immunomodulation.
Clin Cancer Res
; 26(4): 910-921, 2020 02 15.
Article
em En
| MEDLINE
| ID: mdl-31757878
ABSTRACT
PURPOSE:
Radiotherapy (RT) is frequently used for local control of solid tumors using equal dose per fraction. Recently, single high-dose radiation has been used for ablation of solid tumors. In this report, we provide a novel immunological basis for radiation dose fractionation consisting of a single high-dose radiotherapy, followed by postablation modulation (PAM) with four daily low-dose fractions (22 Gy + 0.5 Gy × 4) to reprogram the tumor microenvironment by diminishing immune suppression, enabling infiltration of effector cells and increasing efficacy of tumor control. EXPERIMENTALDESIGN:
Palpable 3LL and 4T1 tumors in C57Bl/6 and Balb/c mice were irradiated with the Small-Animal Radiation Research Platform irradiator, and tumor growth and survival were monitored. Immunomodulation of tumor and immune cells in vitro and in vivo characterization of tumor-infiltrating immune effector cells were performed by FACS. For systemic application of PAM-RT, whole-lung irradiation was administered in 4T1-bearing Balb/c mice.RESULTS:
We report significant tumor growth delays and increased survival in 3LL tumor-bearing mice with PAM. Primary tumor PAM-RT increased infiltration of immune effector cells and decreased Treg in irradiated tumors and secondary lymphoid organs. In a model of murine metastatic breast cancer (4T1), we demonstrated that systemic PAM-RT to the whole lung, 12 days after primary tumor ablative radiotherapy, increased survival with suppression of pulmonary metastases.CONCLUSIONS:
We provide a novel immunologic basis for radiation dose fractionation consisting of a single high dose of radiotherapy followed by daily low-dose PAM-RT fractionation to improve the immunogenic potential of ablative radiotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos do Interstício Tumoral
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Carcinoma Pulmonar de Lewis
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Microambiente Tumoral
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Neoplasias Mamárias Experimentais
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article