Evertine Wesselink, Claire E Thomas, Yasutoshi Takashima, Hiroki Mizuno, Daniel D Buchanan, Conghui Qu, Li Hsu, Andressa Dias Costa, Satoko Ugai, Yuxue Zhong, Jeroen R Huyghe, Sushma Thomas, Steven Gallinger, Robert C Grant, Loïc Le Marchand, Yohei Masugi, Fränzel Jb van Duijnhoven, Tomotaka Ugai, Shuji Ogino, Jonathan A Nowak, Ulrike Peters, Amanda I Phipps
{"title":"结直肠肿瘤中钙摄入与T细胞浸润的关系","authors":"Evertine Wesselink, Claire E Thomas, Yasutoshi Takashima, Hiroki Mizuno, Daniel D Buchanan, Conghui Qu, Li Hsu, Andressa Dias Costa, Satoko Ugai, Yuxue Zhong, Jeroen R Huyghe, Sushma Thomas, Steven Gallinger, Robert C Grant, Loïc Le Marchand, Yohei Masugi, Fränzel Jb van Duijnhoven, Tomotaka Ugai, Shuji Ogino, Jonathan A Nowak, Ulrike Peters, Amanda I Phipps","doi":"10.1158/1940-6207.CAPR-25-0023","DOIUrl":null,"url":null,"abstract":"<p><p>Higher T cell infiltration in colorectal tumours has been associated with better prognosis. Evidence indicates that calcium signalling is essential for T cells functioning. However, as it is unknown whether calcium intake influences T cell infiltration, we investigated the association of calcium intake with T cell subsets in the tumour microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumour infiltrating T cells and calcium intake was available, were included for these analyses. Immune cell infiltration was quantified by digital image analyses with machine learning algorithms using a customized 9-plex multispectral immunofluorescence assay (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, DAPI). Associations between pre-diagnostic calcium intake and densities of non-overlapping subsets of epithelial and stromal tissue area T cells were assessed using multivariable binary or ordinal logistic regression analyses. A higher dietary calcium intake was positively associated with CD3+CD4-CD8- double negative T cells density in the epithelial (OR 1.57; 95% CI 1.13-2.24) and stromal (OR 1.24; 95%CI 1.06-1.45) tumour tissue area. No other statistically significant associations were observed after correcting for multiple testing. In conclusion, dietary calcium intake was associated with a higher density of CD4-CD8- double negative T cells in the epithelial and stromal tumour tissue area, but not with infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumour immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Associations between calcium intake and T cell infiltration in colorectal tumours.\",\"authors\":\"Evertine Wesselink, Claire E Thomas, Yasutoshi Takashima, Hiroki Mizuno, Daniel D Buchanan, Conghui Qu, Li Hsu, Andressa Dias Costa, Satoko Ugai, Yuxue Zhong, Jeroen R Huyghe, Sushma Thomas, Steven Gallinger, Robert C Grant, Loïc Le Marchand, Yohei Masugi, Fränzel Jb van Duijnhoven, Tomotaka Ugai, Shuji Ogino, Jonathan A Nowak, Ulrike Peters, Amanda I Phipps\",\"doi\":\"10.1158/1940-6207.CAPR-25-0023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Higher T cell infiltration in colorectal tumours has been associated with better prognosis. 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引用次数: 0
摘要
结直肠肿瘤中较高的T细胞浸润与较好的预后相关。有证据表明钙信号对T细胞的功能至关重要。然而,由于钙摄入是否影响T细胞浸润尚不清楚,我们研究了钙摄入与结直肠癌肿瘤微环境中T细胞亚群的关系。这些分析总共纳入了来自三个队列研究的943名参与者,这些研究有肿瘤浸润性T细胞和钙摄入量的数据。采用定制的9路多光谱免疫荧光法(CD3、CD4、CD8、CD45RA、CD45RO、FOXP3、KRT、MKI67、DAPI),通过数字图像分析和机器学习算法定量免疫细胞浸润。使用多变量二元或有序logistic回归分析评估诊断前钙摄入量与上皮和间质组织区域T细胞非重叠亚群密度之间的关系。较高的膳食钙摄入量与上皮细胞中CD3+CD4-CD8-双阴性T细胞密度呈正相关(OR 1.57;95% CI 1.13-2.24)和基质(OR 1.24;95%CI 1.06-1.45)肿瘤组织面积。经多重检验校正后,未观察到其他统计学上显著的关联。综上所述,膳食钙摄入与上皮和间质肿瘤组织区域CD4-CD8-双阴性T细胞密度升高有关,但与CD4+或CD8+ T细胞浸润无关。需要更多的研究来进一步阐明钙在肿瘤免疫谱中的作用及其与临床结果的关联。我们的发现为进一步的研究提供了有希望的基础。
Associations between calcium intake and T cell infiltration in colorectal tumours.
Higher T cell infiltration in colorectal tumours has been associated with better prognosis. Evidence indicates that calcium signalling is essential for T cells functioning. However, as it is unknown whether calcium intake influences T cell infiltration, we investigated the association of calcium intake with T cell subsets in the tumour microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumour infiltrating T cells and calcium intake was available, were included for these analyses. Immune cell infiltration was quantified by digital image analyses with machine learning algorithms using a customized 9-plex multispectral immunofluorescence assay (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, DAPI). Associations between pre-diagnostic calcium intake and densities of non-overlapping subsets of epithelial and stromal tissue area T cells were assessed using multivariable binary or ordinal logistic regression analyses. A higher dietary calcium intake was positively associated with CD3+CD4-CD8- double negative T cells density in the epithelial (OR 1.57; 95% CI 1.13-2.24) and stromal (OR 1.24; 95%CI 1.06-1.45) tumour tissue area. No other statistically significant associations were observed after correcting for multiple testing. In conclusion, dietary calcium intake was associated with a higher density of CD4-CD8- double negative T cells in the epithelial and stromal tumour tissue area, but not with infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumour immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research.