Institute of Anatomy, University of Bern, Bern, Switzerland.
Institute of Anatomy, University of Bern, Bern, Switzerland; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):478-493. doi: 10.1016/j.ijrobp.2022.06.090. Epub 2022 Aug 5.
Synchrotron-generated microbeam radiation therapy (MRT) represents an innovative preclinical type of cancer radiation therapy with an excellent therapeutic ratio. Beyond local control, metastatic spread is another important endpoint to assess the effectiveness of radiation therapy treatment. Currently, no data exist on an association between MRT and metastasis. Here, we evaluated the ability of MRT to delay B16F10 murine melanoma progression and locoregional metastatic spread.
We assessed the primary tumor response and the extent of metastasis in sentinel lymph nodes in 2 cohorts of C57BL/6J mice, one receiving a single MRT and another receiving 2 MRT treatments delivered with a 10-day interval. We compared these 2 cohorts with synchrotron broad beam-irradiated and nonirradiated mice. In addition, using multiplex quantitative platforms, we measured plasma concentrations of 34 pro- and anti-inflammatory cytokines and frequencies of immune cell subsets infiltrating primary tumors that received either 1 or 2 MRT treatments.
Two MRT treatments were significantly more effective for local control than a single MRT. Remarkably, the second MRT also triggered a pronounced regression of out-of-radiation field locoregional metastasis. Augmentation of CXCL5, CXCL12, and CCL22 levels after the second MRT indicated that inhibition of melanoma progression could be associated with increased activity of antitumor neutrophils and T-cells. Indeed, we demonstrated elevated infiltration of neutrophils and activated T-cells in the tumors after the second MRT.
Our study highlights the importance of monitoring metastasis after MRT and provides the first MRT fractionation schedule that promotes local and locoregional control with the potential to manage distant metastasis.
同步加速器产生的微束放射治疗（MRT）代表了一种具有优异治疗比的创新临床前癌症放射治疗类型。除了局部控制外，转移扩散是另一个评估放射治疗效果的重要终点。目前，尚无 MRT 与转移之间存在关联的数据。在这里，我们评估了 MRT 延迟 B16F10 小鼠黑色素瘤进展和局部区域转移扩散的能力。
我们评估了 2 组 C57BL/6J 小鼠的原发肿瘤反应和前哨淋巴结转移程度，一组接受单次 MRT，另一组接受 10 天间隔的 2 次 MRT 治疗。我们将这两组与同步加速器宽束照射和未照射的小鼠进行了比较。此外，我们使用多重定量平台测量了接受 1 次或 2 次 MRT 治疗的原发肿瘤中浸润的免疫细胞亚群的血浆中 34 种促炎和抗炎细胞因子的浓度和频率。
两次 MRT 治疗对局部控制的效果明显优于单次 MRT。值得注意的是，第二次 MRT 还引发了辐射场外局部区域转移的明显消退。第二次 MRT 后 CXCL5、CXCL12 和 CCL22 水平的升高表明，抑制黑色素瘤进展可能与抗肿瘤中性粒细胞和 T 细胞活性增加有关。事实上，我们证明了第二次 MRT 后肿瘤中中性粒细胞和活化 T 细胞的浸润增加。
我们的研究强调了监测 MRT 后转移的重要性，并提供了首次促进局部和局部区域控制并有可能管理远处转移的 MRT 分割方案。
