Abstract：
The absolute lymphocyte count (ALC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR) offer convenient means to assess systemic inflammation post-cancer treatment, which influences treatment outcomes. Understanding these biomarker variations and leukocyte subpopulation interplay is crucial for optimizing radiotherapy. Herein, leukocyte subpopulations (T-CD4+, T-CD8+, B-cells, NK-cells, neutrophils, monocytes) during and after brain irradiation (using X-rays or Protons) in tumor-free mice were used to compute ALC, LMR, and NLR, on which radiation parameter influence was assessed by principal component analysis (PCA). NLR kinetics were further examined using modeling. Leukocyte subpopulations interplays and their response to radiation parameters were examined using PCA and correlation analysis. Under X-rays, ALC and LMR decreased, with ALC recovered to baseline after irradiation, but not LMR. Both X-rays and protons increased the NLR during irradiation, recovering in protons but not X-rays. Both irradiation volume and dose rate had a pronounced effect on the NLR. Leukocyte subpopulation interplay was observed under X-rays and protons, normalizing in the proton group by day 28. Lymphopenia was observed in all lymphocyte subpopulations under X-ray irradiation but not protons. The recovery patterns varied among the subpopulations. Neutrophil counts increased during irradiation, with the recovery of protons, but not X-rays, by day 28. Interplays between NK-cells and myeloid subpopulations were evident under X-rays but not protons. Importantly, no interplay was detected between myeloid cells and T/B-cells, indicating that LMR and NLR variations were primarily due to independent responses to brain irradiation. A tumor-free experimental mouse model was used to study the effects of brain radiotherapy on systemic immunity. When administering fractionated irradiation with a total dose of 20 Gy using a vertical beam to either the whole brain or hemi-brain, proton irradiation had fewer adverse impacts on the immune system compared to X-rays in tumor-free rodents.
摘要：
绝对淋巴细胞计数（ALC），淋巴细胞与单核细胞比率（LMR），中性粒细胞与淋巴细胞比率（NLR）为评估癌症治疗后的全身性炎症提供了方便的方法，影响治疗结果。了解这些生物标志物的变化和白细胞亚群的相互作用对于优化放射治疗至关重要。在这里，白细胞亚群（T-CD4+，T-CD8+,B细胞,NK细胞，中性粒细胞，单核细胞）在无瘤小鼠的脑照射（使用X射线或质子）期间和之后用于计算ALC，LMR,和NLR，通过主成分分析(PCA)评估辐射参数的影响。使用建模进一步检查NLR动力学。使用PCA和相关分析检查了白细胞亚群的相互作用及其对辐射参数的反应。在X光下,ALC和LMR下降，照射后ALC恢复到基线，但不是LMR.X射线和质子在辐照过程中都增加了NLR，在质子中恢复，而不是X射线。辐照体积和剂量率均对NLR有明显影响。在X射线和质子下观察到白细胞亚群相互作用，在第28天的质子群中正常化。在X射线照射下，所有淋巴细胞亚群均观察到淋巴细胞减少，但未观察到质子。恢复模式在亚群之间有所不同。照射期间中性粒细胞计数增加，随着质子的回收，但不是X光片,第28天NK细胞和骨髓亚群之间的相互作用在X射线下很明显，但在质子下却没有。重要的是,在骨髓细胞和T/B细胞之间没有检测到相互作用，表明LMR和NLR变化主要是由于对脑照射的独立反应。无瘤实验小鼠模型用于研究脑放疗对全身免疫的影响。当使用垂直光束对全脑或半脑进行总剂量为20Gy的分次照射时，在无肿瘤的啮齿动物中,与X射线相比,质子照射对免疫系统的不利影响较小.
