Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Int J Exp Pathol. 2019 Oct;100(5-6):304-310. doi: 10.1111/iep.12341. Epub 2020 Jan 29.
The aim of the present study was to investigate the correlation between the density of infiltrating T cells and macrophages in the parental colorectal cancer (CRC) and the growth rate of tumoroids (i.e. a patient-derived in vitro 3D model). Tumoroids were established from fresh specimens of primary and metastatic CRC from 29 patients. The in vitro growth rate of tumoroids was monitored by automated imaging. The density of infiltrating T cells and macrophages was determined in the centre of the tumour (CT) and at the invasive margin (IM) of the parental tumours. This was performed by digital image analysis on the whole-slide scanned images using Visiopharm software. Tumoroids with higher density of infiltrating CD3+ lymphocytes in the IM of their parental tumour showed a higher growth rate (P < .0005). The average relative growth rate (log10) during the period from day 1 to day 11 was 0.364 ± 0.006 (mean ± SD) for the CD3+ (IM)-high group and 0.273 ± 0.008 (mean ± SD) for the CD3+ (IM)-low group. In contrast, the density of CD68+ infiltrating macrophages in the parental tumours showed significant inverse effect on the growth rate of the tumoroids (P < .0005). The present study showed that the density of immune cells in the parental CRC correlates with the growth rate of the tumoroids. The future perspective for such a 3D model could be in vitro investigations of the tumour-associated inflammatory microenvironment as well as personalized cancer immunotherapy.
本研究旨在探讨浸润性 T 细胞和巨噬细胞在原发性结直肠癌(CRC)中的密度与肿瘤球(即患者来源的体外 3D 模型)生长速度之间的相关性。肿瘤球是从 29 名患者的原发性和转移性 CRC 新鲜标本中建立的。通过自动成像监测肿瘤球的体外生长速度。在肿瘤的中心(CT)和侵袭边缘(IM)处测定肿瘤亲本中浸润性 T 细胞和巨噬细胞的密度。使用 Visiopharm 软件对全幻灯片扫描图像进行数字图像分析来完成此操作。其亲本肿瘤 IM 中浸润性 CD3+淋巴细胞密度较高的肿瘤球显示出更高的生长速度(P<.0005)。在从第 1 天到第 11 天的时间段内,CD3+(IM)-高组的平均相对生长率(log10)为 0.364±0.006(平均值±标准差),CD3+(IM)-低组为 0.273±0.008(平均值±标准差)。相比之下,亲本肿瘤中 CD68+浸润性巨噬细胞的密度对肿瘤球的生长速度有显著的反向影响(P<.0005)。本研究表明,CRC 中免疫细胞的密度与肿瘤球的生长速度相关。这种 3D 模型的未来前景可能是体外研究肿瘤相关的炎症微环境以及个性化癌症免疫治疗。