X-ray irradiation negatively affects immune responses in the lymphatic network.

Autor: Kanabuchi S; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan., Kitamura N; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Takano-Kasuya M; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Inose T; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Nishidate C; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Yamanashi M; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Kudo M; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Ito T; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Ito N; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan., Okamoto H; Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan., Taniyama Y; Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan., Kobayashi Y; Department of Materials Science and Engineering, Graduate School of Science and Engineering, Ibaraki University, 4-12-1 Nakanarusawacho, Hitachi, Ibaraki 316-8511, Japan., Kamei T; Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan., Gonda K; Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; International Center for Synchrotron Radiation Innovation Smart (SRIS), Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address: gonda@med.tohoku.ac.jp.
Jazyk: angličtina
Zdroj: Microvascular research [Microvasc Res] 2023 Jul; Vol. 148, pp. 104511. Date of Electronic Publication: 2023 Feb 22.
DOI: 10.1016/j.mvr.2023.104511
Abstrakt: Immune checkpoint inhibitor therapy has been attracting attention as a new cancer treatment and is likely to be widely used in combination with radiotherapy. Therefore, examination of the effects of X-ray irradiation on sentinel lymph nodes and lymphatic vessels, which are involved in antigen presentation, is important for therapy. The hindlimbs of mice were irradiated with X-rays (total radiation doses: 2, 10, and 30 Gy), and X-ray computed tomography (CT) imaging was performed using 15-nm or 2-nm gold nanoparticles (AuNPs) as contrast agents on days 7, 14, and 28 after irradiation to evaluate the diameter of the collecting lymph vessels and lymph flow within the irradiated area. X-ray CT imaging data using 15-nm AuNPs on day 28 after irradiation showed that the diameter of the collecting lymph vessels was significantly larger in all irradiated groups compared to the control group (p ≤ 0.01). CT imaging with 2-nm AuNPs showed that lymphatic drainage was significantly reduced in the lymph nodes irradiated with 10 Gy and 30 Gy compared to the lymph nodes irradiated with 2 Gy (p ≤ 0.05). Additionally, immunohistochemical analyses were conducted to evaluate the area density and morphology of high endothelial venules (HEVs) in the lymph nodes, which are important vessels for naive T cells to enter the lymph nodes. The expression level of MECA-79, which specifically localized to HEVs, was significantly decreased in the 10 Gy and 30 Gy irradiation groups compared to the control group (p ≤ 0.05). There was a significant decrease in normal HEV morphology (p ≤ 0.05) and a significant increase in abnormal HEV morphology (p ≤ 0.05) in all irradiated groups. These results also showed that X-ray irradiation induced a time- and radiation dose-dependent increase in the diameter of the collecting lymph vessels, stagnation of intralymphatic lymph flow, and a reduction in the area density of HEVs and their abnormal morphology, demonstrating that X-ray irradiation affected the immune responses. Therefore, these findings suggest that X-ray irradiation to lymph nodes may impair the opportunity for antigen presentation in the lymph nodes, which is the key to cancer immunity, and that for this reason, it is important to carefully plan irradiation of sentinel lymph nodes and develop treatment strategies according to future treatment options.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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