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  • [Cancer Biother Radiopharm.] Evaluation of Radiotherapy-Induced Systemic Antitumor Effects in Mice Bearing 4T1 Mouse Breast Cancer Cells

    동국대 / 권연석, 장현수*

  • 출처
    Cancer Biother Radiopharm.
  • 등재일
    2020 Dec 1.
  • 저널이슈번호
    doi: 10.1089/cbr.2020.3958. Online ahead of print.
  • 내용

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    Abstract
    Background: Recently, several clinical studies have reported that combination treatments of radiation therapy (RT) and immunotherapy in patients with multiple lesions can improve tumor regression at a distance from the irradiated site, known as the abscopal effect. However, when RT and immunotherapy are concurrently applied, it is hard to distinguish the pure systemic effects of RT from those of the immunotherapy drug. In this preclinical study, the authors investigated the systemic antitumor effects of RT alone according to fraction dose size and splitting schedules. Materials and Methods: 4T1 mouse breast cancer cells were implanted into the right and left sides of mammary gland fat pads of BALB/c mice, followed by irradiation with 6 Gy × 3, 8 Gy × 2, and 13 Gy × 1 fractions when the right-side tumors were palpable. Results: The different irradiation schedules produced similar antitumor effects in irradiated right-side tumors and unirradiated left-side tumors. However, 8 Gy × 2 and 13 Gy × 1 fractions exhibited better antimetastatic potential than that from irradiation using 6 Gy × 3 fractions. Furthermore, 8 Gy × 2 and 13 Gy × 1 fractions produced higher expressions of HMGB1 and lower expressions of the proinflammatory cytokines, IFN-γ, TNF-α, IL-6, and IL-1β, from the irradiated tumor tissues. Conclusions: These findings suggest that 8 Gy × 2 and 13 Gy × 1 fractions can provide better systemic antitumor effects than 6 Gy × 3 fractions. The authors hope these results provide clues to optimize RT dose regimens to make the abscopal effect clinically more relevant in future combination treatments.

     

     

    Affiliations

    Yun-Suk Kwon  1 , Min-Gu Lee  1 , Junyoung Baek  1 , Kyung-Soo Nam  1 , Jong Im Lee  2 , Soyoung Kim  1 , Hyunsoo Jang  3
    1 Department of Pharmacology, School of Medicine, Dongguk University, Gyeongju, Republic of Korea.
    2 Department of Pathology, School of Medicine, Dongguk University, Gyeongju, Republic of Korea.
    3 Department of Radiation Oncology, School of Medicine, Dongguk University, Gyeongju, Republic of Korea.

  • 키워드
    4T1 breast cancer cells; abscopal effects; cytokines; damage-associated molecular patterns; metastasis; radiation therapy.
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