"Towards melanoma in situ vaccination with multiple ultra-narrow X-ray beams".

IF 9.1 1区 医学 Q1 ONCOLOGY Cancer letters Pub Date : 2024-11-13 DOI:10.1016/j.canlet.2024.217326
Verdiana Trappetti, Cristian Fernández-Palomo, Prateek Arora, Marine Potez, Paolo Pellicioli, Jennifer Fazzari, Nahoko Shintani, Ismael Sanchez-Gonzalez, Cheuk Ting Wu, Bettina de Breuyn Dietler, Nadia Mercader-Huber, Olga A Martin, Stephan von Gunten, Vladislav Volarevic, Valentin Djonov
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Abstract

Despite the recent progress, current treatment modalities are not able to eradicate cancer. We show that Microbeam Radiotherapy (MRT), an innovative type of Spatially Fractionated Radiotherapy, can control murine melanoma by activating the host's own immune system. The beneficial effects are very pronounced in comparison to uniform radiotherapy, traditionally employed in the clinic. Our results displayed that MRT increased antigen presentation, activating Cytotoxic T Lymphocytes (CTLs) which are essential to MRT's treatment efficacy in melanoma. Depletion of CTLs abrogated treatment response. Multiplex nucleic acid hybridization technology revealed key features of lymphocyte populations such as proliferation, differentiation, and ligand-receptor interactions. In addition, CTLs were shown to be essential for locoregional metastatic control and systemic abscopal effects confirmed by activation of antigen presenting cells and CTL trafficking in the tumour-draining lymph nodes. MRT induces a robust antitumour immune response, matching the characteristics of in situ vaccination, that could be exploited to treat a variety of treatment-resistant malignancies.

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"利用多束超窄 X 射线实现黑色素瘤原位接种"。
尽管取得了最新进展,但目前的治疗方法仍无法根除癌症。我们的研究表明,微束放疗(MRT)是一种创新的空间分次放疗,它可以通过激活宿主自身的免疫系统来控制小鼠黑色素瘤。与临床上传统采用的均匀放疗相比,这种疗法的有益效果非常明显。我们的研究结果表明,MRT 增加了抗原呈递,激活了细胞毒性 T 淋巴细胞(CTLs),而 CTLs 是 MRT 对黑色素瘤疗效的关键。CTL的耗竭会减弱治疗反应。多重核酸杂交技术揭示了淋巴细胞群的关键特征,如增殖、分化和配体-受体相互作用。此外,抗原呈递细胞的活化和肿瘤引流淋巴结中 CTL 的贩运证实,CTL 对局部转移控制和全身脱落效应至关重要。MRT能诱导强大的抗肿瘤免疫反应,符合原位疫苗接种的特点,可用于治疗各种耐药恶性肿瘤。
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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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