Loss of Skeletal Muscle Mass Is Associated With Reduced Cytotoxic T Cell Abundance and Poor Survival in Advanced Lung Cancer

IF 9.1 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-09-10 DOI:10.1002/jcsm.70063

Xin Nie, Yan Sun, David P. J. van Dijk, Min Deng, Ralph Brecheisen, Zhaoqi Wang, Qingxin Xia, Steven M. W. Olde Damink, Sander S. Rensen

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Abstract

Background

Body composition alterations such as skeletal muscle (SM) loss in cancer patients are associated with poor survival. In turn, immune cell-driven pathways have been linked to muscle wasting. We aimed to investigate the relationship between body composition, tumour-infiltrating lymphocytes and survival in patients with advanced lung cancer.

Methods

We studied 200 patients with advanced lung cancer receiving immunotherapy (n = 81) or non-immunotherapy regimens (n = 119). Body composition including SM index (SMI) at baseline and longitudinal changes were assessed using computed tomography (CT) scans at the third lumbar vertebra. Associations between body composition parameters and overall survival (OS) were evaluated using Cox regression analysis. The median value of SMI, stratified by sex, was used as the cut-off to define groups with high and low baseline SMI. Stable SMI was defined by any increase or < 2% decrease per 100 days; loss of SMI was defined by ≥ 2% decrease per 100 days. Logistic regression analysis was applied to investigate the association between SMI and peripheral circulating immune cells. Tumour-infiltrating lymphocytes were identified by immunohistochemistry, and their relationship with SMI was evaluated.

Results

SMI loss was associated with shorter OS (whole cohort: HR = 2.314, 95% CI = 1.388–3.858, p = 0.001; immunotherapy cohort: HR = 3.028, 95% CI = 1.113–8.236, p = 0.03; non-immunotherapy cohort: HR = 2.298, 95% CI = 1.191–4.435, p = 0.013). Low baseline SMI was associated with higher CD3⁺ T cell abundance (OR = 1.240, 95% CI = 1.080–1.424, p = 0.002) but lower CD3⁺ CD8⁺ T cell abundance (OR = 0.862, 95% CI = 0.762–0.974, p = 0.018) in peripheral blood. Subsequent SMI loss during treatment was also significantly associated with higher CD3⁺ T cell counts (OR = 3.414, 95% CI = 1.301–8.961, p = 0.013) and lower CD3⁺ CD8⁺ T cell abundance (OR = 0.666, 95% CI = 0.459–0.968, p = 0.033). Patients with stable SMI had a higher number of CD8⁺ tumour-infiltrating lymphocytes than patients with SMI loss (15.4% vs. 7.9%, p = 0.036).

Conclusion

SM loss is an independent predictor for survival in patients with advanced lung cancer and is associated with reduced peripheral and tumour-infiltrating cytotoxic T cell abundance. An inadequate antitumour immune response may contribute to metabolic tissue wasting in cancer.

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晚期肺癌骨骼肌质量损失与细胞毒性T细胞丰度降低和生存率低相关

背景：癌症患者骨骼肌（SM）损失等身体组成改变与较差的生存率相关。反过来，免疫细胞驱动的途径与肌肉萎缩有关。我们旨在探讨晚期肺癌患者机体组成、肿瘤浸润淋巴细胞与生存的关系。方法研究200例晚期肺癌患者，分别接受免疫治疗（81例）和非免疫治疗（119例）。通过第三腰椎的计算机断层扫描（CT）评估身体组成，包括基线时的SM指数（SMI）和纵向变化。采用Cox回归分析评估体成分参数与总生存期（OS）之间的关系。SMI的中位数，按性别分层，被用作定义高和低基线SMI组的截止值。稳定型SMI定义为每100天增加或减少< 2%；SMI的丧失定义为每100天下降≥2%。采用Logistic回归分析探讨SMI与外周血循环免疫细胞的关系。免疫组化法鉴定肿瘤浸润淋巴细胞，并评价其与重度精神分裂症的关系。结果smi丧失与较短的生存期相关（全队列：HR = 2.314, 95% CI = 1.388 ~ 3.858, p = 0.001；免疫治疗组：HR = 3.028, 95% CI = 1.113 ~ 8.236, p = 0.03；非免疫治疗组：HR = 2.298, 95% CI = 1.191 ~ 4.435, p = 0.013）。低基线SMI与外周血中较高的CD3+ T细胞丰度（OR = 1.240, 95% CI = 1.080-1.424, p = 0.002）和较低的CD3+ CD8+ T细胞丰度（OR = 0.862, 95% CI = 0.762-0.974, p = 0.018）相关。治疗期间的SMI丢失也与CD3+ T细胞计数升高（OR = 3.414, 95% CI = 1.301-8.961, p = 0.013）和CD3+ CD8+ T细胞丰度降低（OR = 0.666, 95% CI = 0.459-0.968, p = 0.033）显著相关。稳定型重度抑郁患者的CD8+肿瘤浸润淋巴细胞数量高于重度抑郁患者（15.4% vs. 7.9%, p = 0.036）。结论sm丢失是晚期肺癌患者生存的独立预测因子，与外周和肿瘤浸润性细胞毒性T细胞丰度降低有关。不充分的抗肿瘤免疫反应可能导致癌症中代谢组织的浪费。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.