Anna Ubink , Marieke R. ten Tusscher , Hans J. van der Vliet , Joeri A.J. Douma , Tanja D. de Gruijl , Hetty Bontkes , Petra Bonnet , Diede van Ens , Willemijn Hobo , Harry Dolstra , Ellis Barbé , Susanne van der Velde , Catharina Willemien Menke-van der Houven van Oordt , Simone H.C. Havenith , Annemarie Conijn-Mensink , Annette A. van Zweeden , Harm Westdorp , Joannes F.M. Jacobs , Laurien M. Buffart
{"title":"探讨运动对接受新辅助化疗的乳腺癌患者免疫细胞功能和肿瘤浸润的影响-一项可行性试验","authors":"Anna Ubink , Marieke R. ten Tusscher , Hans J. van der Vliet , Joeri A.J. Douma , Tanja D. de Gruijl , Hetty Bontkes , Petra Bonnet , Diede van Ens , Willemijn Hobo , Harry Dolstra , Ellis Barbé , Susanne van der Velde , Catharina Willemien Menke-van der Houven van Oordt , Simone H.C. Havenith , Annemarie Conijn-Mensink , Annette A. van Zweeden , Harm Westdorp , Joannes F.M. Jacobs , Laurien M. Buffart","doi":"10.1016/j.bbih.2025.101021","DOIUrl":null,"url":null,"abstract":"<div><div>Pre-clinical studies have shown that exercise can decrease tumour growth through mobilisation, activation, and increased tumour infiltration of natural killer (NK) and CD8<sup>+</sup> T cells. It is currently unclear whether this can be extrapolated to patients. Therefore, a pilot study was set up to examine the feasibility of obtaining an additional study biopsy and to generate preliminary data on the potential effects of exercise on peripheral immune cell function and tumour immune infiltration. Twenty patients with stage I-III breast cancer receiving neoadjuvant chemotherapy were included (participation rate: 27%). Patients were randomised into the intervention group receiving a six-week supervised aerobic and resistance exercise program or the control group. Blood samples and tumour biopsies were collected before randomisation and after six weeks of chemotherapy. For 8 of 20 (40%) patients, we were able to obtain and analyse biopsies at diagnosis and six-week follow-up. This showed a decrease in CD56<sup>+</sup> cells/mm<sup>2</sup> tumour tissue in the three patients of the control group, while it remained stable in most patients of the exercise group. Upon co-culture of peripheral blood mononuclear cells with K562 tumour cells, the exercise group showed increased expression of the degranulation marker CD107a on NK cells (β = 1038.5, 95%CI = 56.9; 2020.2, p = 0.04), and a trend towards increased tumour cell lysis <em>in vitro</em> (β = 18.8%, 95%CI = −3.9; 41.5, p = 0.10) compared to the control group. In conclusion, the study design was feasible with regard to the participation rate, however, revision is needed with regard to the use of a study-related biopsy prior to a sufficiently powered randomised controlled trial.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101021"},"PeriodicalIF":3.7000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the effects of exercise on immune cell function and tumour infiltration in patients with breast cancer receiving neoadjuvant chemotherapy – a feasibility trial\",\"authors\":\"Anna Ubink , Marieke R. ten Tusscher , Hans J. van der Vliet , Joeri A.J. Douma , Tanja D. de Gruijl , Hetty Bontkes , Petra Bonnet , Diede van Ens , Willemijn Hobo , Harry Dolstra , Ellis Barbé , Susanne van der Velde , Catharina Willemien Menke-van der Houven van Oordt , Simone H.C. Havenith , Annemarie Conijn-Mensink , Annette A. van Zweeden , Harm Westdorp , Joannes F.M. Jacobs , Laurien M. Buffart\",\"doi\":\"10.1016/j.bbih.2025.101021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Pre-clinical studies have shown that exercise can decrease tumour growth through mobilisation, activation, and increased tumour infiltration of natural killer (NK) and CD8<sup>+</sup> T cells. It is currently unclear whether this can be extrapolated to patients. Therefore, a pilot study was set up to examine the feasibility of obtaining an additional study biopsy and to generate preliminary data on the potential effects of exercise on peripheral immune cell function and tumour immune infiltration. Twenty patients with stage I-III breast cancer receiving neoadjuvant chemotherapy were included (participation rate: 27%). Patients were randomised into the intervention group receiving a six-week supervised aerobic and resistance exercise program or the control group. Blood samples and tumour biopsies were collected before randomisation and after six weeks of chemotherapy. For 8 of 20 (40%) patients, we were able to obtain and analyse biopsies at diagnosis and six-week follow-up. This showed a decrease in CD56<sup>+</sup> cells/mm<sup>2</sup> tumour tissue in the three patients of the control group, while it remained stable in most patients of the exercise group. Upon co-culture of peripheral blood mononuclear cells with K562 tumour cells, the exercise group showed increased expression of the degranulation marker CD107a on NK cells (β = 1038.5, 95%CI = 56.9; 2020.2, p = 0.04), and a trend towards increased tumour cell lysis <em>in vitro</em> (β = 18.8%, 95%CI = −3.9; 41.5, p = 0.10) compared to the control group. In conclusion, the study design was feasible with regard to the participation rate, however, revision is needed with regard to the use of a study-related biopsy prior to a sufficiently powered randomised controlled trial.</div></div>\",\"PeriodicalId\":72454,\"journal\":{\"name\":\"Brain, behavior, & immunity - health\",\"volume\":\"46 \",\"pages\":\"Article 101021\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, behavior, & immunity - health\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666354625000791\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, behavior, & immunity - health","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666354625000791","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
临床前研究表明,运动可以通过动员、激活和增加自然杀伤细胞(NK)和CD8+ T细胞的肿瘤浸润来减少肿瘤的生长。目前尚不清楚这是否可以外推到患者身上。因此,建立了一项试点研究,以检查获得额外研究活检的可行性,并产生关于运动对周围免疫细胞功能和肿瘤免疫浸润的潜在影响的初步数据。纳入20例接受新辅助化疗的I-III期乳腺癌患者(参与率:27%)。患者被随机分为干预组和对照组,干预组接受为期六周的有氧和阻力运动计划。在随机分组前和化疗六周后采集血液样本和肿瘤活检。20例患者中有8例(40%)在诊断和6周随访时获得活组织检查并进行分析。结果显示,在对照组的三名患者中,CD56+细胞/mm2肿瘤组织减少,而在运动组的大多数患者中,CD56+细胞/mm2肿瘤组织保持稳定。外周血单个核细胞与K562肿瘤细胞共培养后,运动组NK细胞上脱颗粒标志物CD107a表达增加(β = 1038.5, 95%CI = 56.9;2020.2, p = 0.04),体外肿瘤细胞溶解增加的趋势(β = 18.8%, 95%CI = - 3.9;41.5, p = 0.10)。总之,就参与率而言,研究设计是可行的,然而,在进行足够有力的随机对照试验之前,需要对研究相关活检的使用进行修订。
Exploring the effects of exercise on immune cell function and tumour infiltration in patients with breast cancer receiving neoadjuvant chemotherapy – a feasibility trial
Pre-clinical studies have shown that exercise can decrease tumour growth through mobilisation, activation, and increased tumour infiltration of natural killer (NK) and CD8+ T cells. It is currently unclear whether this can be extrapolated to patients. Therefore, a pilot study was set up to examine the feasibility of obtaining an additional study biopsy and to generate preliminary data on the potential effects of exercise on peripheral immune cell function and tumour immune infiltration. Twenty patients with stage I-III breast cancer receiving neoadjuvant chemotherapy were included (participation rate: 27%). Patients were randomised into the intervention group receiving a six-week supervised aerobic and resistance exercise program or the control group. Blood samples and tumour biopsies were collected before randomisation and after six weeks of chemotherapy. For 8 of 20 (40%) patients, we were able to obtain and analyse biopsies at diagnosis and six-week follow-up. This showed a decrease in CD56+ cells/mm2 tumour tissue in the three patients of the control group, while it remained stable in most patients of the exercise group. Upon co-culture of peripheral blood mononuclear cells with K562 tumour cells, the exercise group showed increased expression of the degranulation marker CD107a on NK cells (β = 1038.5, 95%CI = 56.9; 2020.2, p = 0.04), and a trend towards increased tumour cell lysis in vitro (β = 18.8%, 95%CI = −3.9; 41.5, p = 0.10) compared to the control group. In conclusion, the study design was feasible with regard to the participation rate, however, revision is needed with regard to the use of a study-related biopsy prior to a sufficiently powered randomised controlled trial.