肿瘤细胞治疗研究
英文原题：The effects of exercise training for eight weeks on immune cell characteristics among breast cancer survivors.
在乳腺癌生存者中，经过 8 周运动训练后，大多数免疫细胞特征相对稳定。
方法：本研究考察治疗结束后两年内的20名乳腺癌幸存者（年龄56±6岁，体质指数25.4±3.0 kg/m²）进行8周运动训练后，血液免疫细胞特征的变化。参与者随机分为部分监督运动组和远程支持运动组（各10人）。部分监督组每周进行2次监督训练（实验室跑步机步行和骑行）及1次无监督训练（户外步行），训练时长从35分钟增加至50分钟，强度从最大摄氧量的55%增加至70%。远程支持组通过每周电话讨论运动追踪器数据并接受运动/户外步行目标，目标从每周105分钟逐渐增加至150分钟，强度为最大摄氧量的55%–70%。采用流式细胞术评估免疫细胞计数，包括CD4+和CD8+ T细胞（通过CD27/CD45RA区分初始、中央记忆、效应和终末分化效应记忆亚型）、干细胞样记忆T细胞（通过CD95/CD127）、B细胞（通过CD19/CD27/CD38/CD10区分浆母、记忆、未成熟和初始细胞）以及NK效应和调节性细胞（通过CD56/CD16区分）。通过静息HLA-DR表达或酶联免疫斑点实验测定T细胞功能；实验中使用病毒或肿瘤相关抗原进行刺激并检测干扰素-γ（IFN-γ）产生。结果：训练后总白细胞、淋巴细胞、单核细胞和中性粒细胞计数未发生变化（p>0.425）。多数CD4+、CD8+ T细胞亚型（包括TSCM）、B细胞和NK细胞亚型也无变化（p>0.127）。不过，合并分析两组后，训练结束时CD4+ EMRA T细胞计数降低（18±33比12±22个/μL，p=0.028），且这些细胞的单细胞活化程度较低（HLA-DR中位荧光强度463±138比420±77，p=0.018）。此外，部分监督组CD4+/CD8+比值显著下降（3.90±2.98比2.54±1.29，p=0.006），调节性NK细胞显著增加（16±8比21±10个/μL，p=0.011）。运动训练未改变T细胞IFN-γ产生（p>0.515）。讨论：总体而言，乳腺癌幸存者经过8周运动训练后，多数免疫细胞特征相对稳定。CD4+ EMRA T细胞计数和活化程度降低，可能反映运动具有抗免疫衰老作用。
METHODS: This study examined the effects of exercise training for 8 weeks on blood immune cell characteristics among 20 breast cancer survivors (age 56 6 years, Body Mass Index 25.4 3.0 kg m 2 ) within two years of treatment. Participants were randomly allocated to a partly-supervised or a remotely-supported exercise group ( n = 10 each). The partly supervised group undertook 2 supervised (laboratory-based treadmill walking and cycling) and 1 unsupervised session per week (outdoor walking) progressing from 35 to 50 min and 55% to 70% V O 2 max. The remotely-supported group received weekly exercise/outdoor walking targets (progressing from 105 to 150 min per week 55% to 70% V O 2 max) via weekly telephone calls discussing data from a fitness tracker. Immune cell counts were assessed using flow cytometry: CD4+ and CD8+ T cells (Na ve, NA; Central memory, CM; and Effector cells, EM and EMRA; using CD27/CD45RA), Stem cell-like memory T cells (TSCMs; using CD95/CD127), B cells (plasmablasts, memory, immature and na ve cells using CD19/CD27/CD38/CD10) and Natural Killer cells (effector and regulatory cells, using CD56/CD16). T cell function was assessed by unstimulated HLA-DR expression or interferon gamma (IFN- ) production with Enzyme-linked ImmunoSpot assays following stimulation with virus or tumour-associated antigens. RESULTS: Total leukocyte counts, lymphocytes, monocytes and neutrophils did not change with training ( p > 0.425). Most CD4+ and CD8+ T cell subtypes, including TSCMs, and B cell and NK cell subtypes did not change ( p > 0.127). However, across groups combined, the CD4+ EMRA T cell count was lower after training (cells/ l: 18 33 vs. 12 22, p = 0.028) and these cells were less activated on a per cell basis (HLA-DR median fluorescence intensity: 463 138 vs. 420 77, p = 0.018). Furthermore, the partly-supervised group showed a significant decrease in the CD4+/CD8+ ratio (3.90 2.98 vs. 2.54 1.29, p = 0.006) and a significant increase of regulatory NK cells (cells/ l: 16 8 vs. 21 10, p = 0.011). T cell IFN- production did not change with exercise training ( p > 0.515). DISCUSSION: In summary, most immune cell characteristics are relatively stable with 8 weeks of exercise training among breast cancer survivors. The lower counts and activation of CD4+ EMRA T cells, might reflect an anti-immunosenescence effect of exercise.
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