San Diego Biomedical Research Institute, San Diego, USA.
Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, University of Washington, Seattle, WA, USA.
J Cachexia Sarcopenia Muscle. 2019 Aug;10(4):827-843. doi: 10.1002/jcsm.12424. Epub 2019 Apr 12.
Tumour growth can promote the loss of muscle mass and function. This is particularly disturbing because overall survival is significantly reduced in people with weaker and smaller skeletal muscle. The risk of cancer is also greater in people who are immune deficient. Muscle wasting in mice with cancer can be inhibited by infusion of CD4 precursor T cells that restore balanced ratios of naïve, memory, and regulatory T cells. These data are consistent with the hypothesis that stronger anti-cancer T cell immunity leads to improved muscle mass and function. As a first step to testing this hypothesis, we determined whether levels of circulating T cell subsets correlate with levels of muscle strength in people with cancer.
The frequency of circulating CD4 and CD8 naïve, memory, and regulatory T cell subsets was quantified in 11 men with gastrointestinal cancer (aged 59.3 ± 10.1 years) and nine men without cancer (aged 60 ± 13 years), using flow cytometry. T cell marker expression was determined using real-time PCR and western blot analyses in whole blood and peripheral blood mononuclear cells. Handgrip strength, one-repetition maximum chest press, and knee extension tests were used to determine muscle strength. Performance was determined using a stair climb test. Body composition was determined using dual-energy X-ray absorptiometry scan. The Karnofsky and ECOG scales were used to assess functional impairment. Correlations between frequencies of cell subsets with strength, performance, and body composition were determined using regression analyses.
Our data show significant correlations between (i) higher frequencies of CD8 naïve (P = 0.02) and effector memory (P = 0.003) T cells and lower frequencies of CD8 central memory T cells (P = 0.002) with stronger handgrip strength, (ii) lower frequency of regulatory cells with greater lean mass index (P = 0.04), (iii) lower frequency of CD8 T cells that express CD95 with greater stair climb power (P = 0.003), (iv) higher frequency of T cells that co-express CD197 and CD45RA and greater one-repetition maximum knee extension strength (P = 0.008), and (iv) higher expression of CD4 in whole blood with greater functional impairment (P = 0.004) in people with cancer.
We have identified significant correlations between levels of T cell populations and muscle strength, performance, and body composition in people with cancer. These data justify a follow-up study with a larger cohort to test the validity of the findings.
肿瘤生长会导致肌肉质量和功能丧失。这尤其令人不安，因为骨骼肌较弱和较小的人总体生存率显著降低。免疫功能低下的人患癌症的风险也更高。输注 CD4 前体 T 细胞可抑制癌症小鼠的肌肉消耗，这些细胞恢复了幼稚、记忆和调节性 T 细胞的平衡比例。这些数据与更强的抗肿瘤 T 细胞免疫可导致改善肌肉质量和功能的假设一致。作为检验该假设的第一步，我们确定了癌症患者循环 T 细胞亚群的水平是否与肌肉力量水平相关。
使用流式细胞术定量测定 11 名胃肠道癌男性（年龄 59.3±10.1 岁）和 9 名无癌症男性（年龄 60±13 岁）的循环 CD4 和 CD8 幼稚、记忆和调节性 T 细胞亚群的频率。使用实时 PCR 和 Western blot 分析在全血和外周血单核细胞中测定 T 细胞标志物表达。使用握力、一次重复最大胸部按压和膝关节伸展测试来确定肌肉力量。使用楼梯攀爬测试来确定性能。使用双能 X 射线吸收法扫描来确定身体成分。使用 Karnofsky 和 ECOG 量表评估功能障碍。使用回归分析确定细胞亚群与力量、性能和身体成分之间的相关性。
我们的数据显示，（i）较高频率的 CD8 幼稚（P=0.02）和效应记忆（P=0.003）T 细胞与较低频率的 CD8 中央记忆 T 细胞（P=0.002）与较强的握力相关，（ii）调节性细胞的频率与更大的瘦体重指数相关（P=0.04），（iii）CD8 T 细胞表达 CD95 的频率与更大的楼梯攀爬功率相关（P=0.003），（iv）共表达 CD197 和 CD45RA 的 T 细胞频率与更大的一次重复最大膝关节伸展强度相关（P=0.008），以及（iv）癌症患者全血中 CD4 的表达与更大的功能障碍相关（P=0.004）。
我们已经确定了癌症患者中 T 细胞群体水平与肌肉力量、性能和身体成分之间存在显著相关性。这些数据证明了在更大的队列中进行后续研究以检验这些发现的有效性是合理的。
