Normandie Univ, UNICAEN, CNRS, ISTCT, GIP Cyceron, Caen, France.
Laboratoire de physique corpusculaire UMR6534 IN2P3/ENSICAEN, France - Normandie Université, France.
Int J Radiat Biol. 2024;100(5):744-755. doi: 10.1080/09553002.2024.2324471. Epub 2024 Mar 11.
Lymphopenia is extensively studied, but not circulating leucocyte subpopulations, which however have distinct roles in tumor tolerance. Proton therapy has been shown to have a lesser impact on the immune system than conventional X-ray radiotherapy through lower dose exposure to healthy tissues. We explored the differential effects of brain X-ray and proton irradiation on circulating leucocyte subpopulations.
Leucocyte subpopulation counts from tumor-free mice were obtained 12 hours after 4 fractions of 2.5 Gy. The relationships between irradiation type (X-rays or protons), irradiated volume (whole-brain/hemi-brain) and dose rate (1 or 2 Gy/min) with circulating leucocyte subpopulations (T-CD4+, T-CD8+, B, and NK-cells, neutrophils, and monocytes) were investigated using linear regression and tree-based modeling approaches. Relationships between dose maps (brain, vessels, lymph nodes (LNs)) and leucocyte subpopulations were analyzed and applied to construct the blood dose model, assessing the hypothesis of a direct lymphocyte-killing effect in radiation-induced lymphopenia.
Radiation-induced lymphopenia occurred after X-ray but not proton brain irradiation in lymphoid subpopulations (T-CD4+, T-CD8+, B, and NK-cells). There was an increase in neutrophil counts following protons but not X-rays. Monocytes remained unchanged under both X-rays and protons. Besides irradiation type, irradiated volume and dose rate had a significant impact on NK-cell, neutrophil and monocyte levels but not T-CD4+, T-CD8+, and B-cells. The dose to the blood had a heterogeneous impact on leucocyte subpopulations: neutrophil counts remained stable with increasing dose to the blood, while lymphocyte counts decreased with increasing dose (T-CD8+-cells > T-CD4+-cells > B-cells > NK-cells). Direct cell-killing effect of the dose to the blood mildly contributed to radiation-induced lymphopenia. LN exposure significantly contributed to lymphopenia and partially explained the distinct impact of irradiation type on circulating lymphocytes.
Leucocyte subpopulations reacted differently to X-ray or proton brain irradiation. This difference could be partly explained by LN exposure to radiation dose. Further researches and analyses on other biological processes and interactions between leucocyte subpopulations are ongoing. The various mechanisms underlying leucocyte subpopulation changes under different irradiation modalities may have implications for the choice of radiotherapy modalities and their combination with immunotherapy in brain cancer treatment.
淋巴细胞减少症已得到广泛研究，但循环白细胞亚群尚未得到研究，而后者在肿瘤耐受中具有独特的作用。质子治疗通过使健康组织接受较低剂量的照射，显示出对免疫系统的影响小于常规 X 射线放射治疗。我们探讨了脑部 X 射线和质子照射对循环白细胞亚群的差异影响。
无肿瘤小鼠在接受 4 次 2.5Gy 分次照射 12 小时后，获得白细胞亚群计数。使用线性回归和基于树的建模方法，研究了照射类型（X 射线或质子）、照射体积（全脑/半脑）和剂量率（1 或 2Gy/min）与循环白细胞亚群（T-CD4+、T-CD8+、B 和 NK 细胞、中性粒细胞和单核细胞）之间的关系。分析了剂量图（脑、血管、淋巴结（LN））与白细胞亚群之间的关系，并将其应用于构建血液剂量模型，评估了放射诱导性淋巴细胞减少症中直接杀伤淋巴细胞的假说。
X 射线但不是质子脑照射会引起淋巴细胞减少症的淋巴亚群（T-CD4+、T-CD8+、B 和 NK 细胞）发生辐射诱导性淋巴细胞减少。质子照射后中性粒细胞计数增加，但 X 射线照射后中性粒细胞计数没有增加。X 射线和质子照射后单核细胞均无变化。除了照射类型外，照射体积和剂量率对 NK 细胞、中性粒细胞和单核细胞水平有显著影响，但对 T-CD4+、T-CD8+和 B 细胞没有影响。血液剂量对白细胞亚群的影响具有异质性：随着血液剂量的增加，中性粒细胞计数保持稳定，而淋巴细胞计数随着剂量的增加而减少（T-CD8+-细胞>T-CD4+-细胞>B 细胞>NK 细胞）。血液剂量的直接细胞杀伤作用对辐射诱导性淋巴细胞减少有一定贡献。LN 暴露对淋巴细胞减少有显著贡献，部分解释了照射类型对循环淋巴细胞的不同影响。
白细胞亚群对 X 射线或质子脑照射的反应不同。这种差异可以部分解释为 LN 对辐射剂量的暴露。正在对其他生物过程和白细胞亚群之间的相互作用进行进一步的研究和分析。不同照射模式下白细胞亚群变化的各种机制可能对放射治疗模式的选择及其与脑癌治疗中免疫疗法的结合具有重要意义。
