Department of Charged Particle Therapy Research, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan.
Department of Charged Particle Therapy Research, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan.
Biochem Biophys Res Commun. 2024 Jul 23;718:150058. doi: 10.1016/j.bbrc.2024.150058. Epub 2024 May 4.
The therapeutic efficacy of radiotherapy (RT) is primarily driven by two factors: biophysical DNA damage in cancer cells and radiation-induced anti-tumor immunity. However, Anti-tumor immune responses between X-ray RT (XRT) and carbon-ion RT (CIRT) remain unclear. In this study, we, employed mouse models to assess the immunological contribution, especially cytotoxic T-lymphocyte (CTL)-mediated immunity, to the therapeutic effectiveness of XRT and CIRT in shrinking tumors. We irradiated mouse intradermal tumors of B16F10-ovalbumin (OVA) mouse melanoma cells and 3LL-OVA mouse lung cancer cells with carbon-ion beams or X-rays in the presence or absence of CTLs. CTL removal was performed by administration of anti-CD8 monoclonal antibody (mAb) in mice. Based on tumor growth delay, we determined the tumor growth and regression curves. The enhancement ratio (ER) of the slope of regression lines in the presence of CTLs, relative to the absence of CTLs, indicates the dependency of RT on CTLs for shrinking mouse tumors, and the biological effectiveness (RBE) of CIRT relative to XRT were calculated. Tumor growth curves revealed that the elimination of CD8 CTLs by administrating anti-CD8 mAb accelerated tumor growth compared to the presence of CTLs in both RTs. The ERs were larger in CIRT compared to XRT in the B16F10-OVA tumor models, but not in the 3LL-OVA models, suggesting a greater contribution of CTL-mediated anti-tumor immunity to tumor reduction in CIRT compared to XRT in the B16F10-OVA tumor model. In addition, the RBE values for both models were larger in the presence of CTLs compared to models without CTLs, suggesting that CIRT may utilize CTL-mediated anti-tumor immunity more than X-ray. The findings from this study suggest that although immunological contribution to therapeutic efficacy may vary depending on the type of tumor cell, CIRT utilizes CTL-mediated immunity to a greater extent compared to XRT.
放射治疗（RT）的疗效主要取决于两个因素：癌细胞中的生物物理 DNA 损伤和放射诱导的抗肿瘤免疫。然而，X 射线 RT（XRT）和碳离子 RT（CIRT）之间的抗肿瘤免疫反应尚不清楚。在这项研究中，我们使用小鼠模型评估了免疫贡献，特别是细胞毒性 T 淋巴细胞（CTL）介导的免疫，以评估 XRT 和 CIRT 在缩小肿瘤方面的治疗效果。我们用碳离子束或 X 射线辐照 B16F10-卵清蛋白（OVA）小鼠黑色素瘤细胞和 3LL-OVA 小鼠肺癌细胞的皮肤内肿瘤，同时存在或不存在 CTL。CTL 的去除是通过在小鼠中给予抗 CD8 单克隆抗体（mAb）来完成的。根据肿瘤生长延迟，我们确定了肿瘤生长和回归曲线。CTL 存在时，回归线斜率的增强比（ER）相对于 CTL 不存在时，表明 RT 依赖 CTL 缩小小鼠肿瘤，并且计算了 CIRT 相对于 XRT 的生物学有效性（RBE）。肿瘤生长曲线表明，与 RT 中存在 CTL 相比，用抗 CD8 mAb 消除 CD8 CTL 会加速肿瘤生长。在 B16F10-OVA 肿瘤模型中，CIRT 的 ER 大于 XRT，但在 3LL-OVA 模型中则不然，这表明在 B16F10-OVA 肿瘤模型中，CIRT 比 XRT 更能促进 CTL 介导的抗肿瘤免疫对肿瘤的减少。此外，与没有 CTL 的模型相比，在存在 CTL 的情况下，两种模型的 RBE 值都更大，这表明 CIRT 可能比 X 射线更能利用 CTL 介导的抗肿瘤免疫。这项研究的结果表明，尽管免疫对治疗效果的贡献可能因肿瘤细胞类型而异，但与 XRT 相比，CIRT 更能利用 CTL 介导的免疫。
