Nearchou Ines P, Gwyther Bethany M, Georgiakakis Elena C T, Gavriel Christos G, Lillard Kate, Kajiwara Yoshiki, Ueno Hideki, Harrison David J, Caie Peter D
1Quantitative and Digital Pathology, School of Medicine, University of St Andrews, St Andrews, KY16 9TF UK.
Indica Labs, Inc, 2469 Corrales Rd Bldg A-3, Corrales, NM 87048 USA.
NPJ Digit Med. 2020 May 15;3:71. doi: 10.1038/s41746-020-0275-x. eCollection 2020.
Cellular subpopulations within the colorectal tumor microenvironment (TME) include CD3 and CD8 lymphocytes, CD68 and CD163 macrophages, and tumor buds (TBs), all of which have known prognostic significance in stage II colorectal cancer. However, the prognostic relevance of their spatial interactions remains unknown. Here, by applying automated image analysis and machine learning approaches, we evaluate the prognostic significance of these cellular subpopulations and their spatial interactions. Resultant data, from a training cohort retrospectively collated from Edinburgh, UK hospitals ( = 113), were used to create a combinatorial prognostic model, which identified a subpopulation of patients who exhibit 100% survival over a 5-year follow-up period. The combinatorial model integrated lymphocytic infiltration, the number of lymphocytes within 50-μm proximity to TBs, and the CD68/CD163 macrophage ratio. This finding was confirmed on an independent validation cohort, which included patients treated in Japan and Scotland ( = 117). This work shows that by analyzing multiple cellular subpopulations from the complex TME, it is possible to identify patients for whom surgical resection alone may be curative.
结直肠癌微环境（TME）中的细胞亚群包括CD3和CD8淋巴细胞、CD68和CD163巨噬细胞以及肿瘤芽（TBs），所有这些在II期结直肠癌中都具有已知的预后意义。然而，它们空间相互作用的预后相关性仍然未知。在这里，通过应用自动图像分析和机器学习方法，我们评估了这些细胞亚群及其空间相互作用的预后意义。从英国爱丁堡医院回顾性整理的一个训练队列（n = 113）中获得的结果数据，被用于创建一个组合预后模型，该模型识别出在5年随访期内生存率为100%的患者亚群。该组合模型整合了淋巴细胞浸润、距离TBs 50μm范围内的淋巴细胞数量以及CD68/CD163巨噬细胞比率。这一发现在一个独立验证队列中得到了证实，该队列包括在日本和苏格兰接受治疗的患者（n = 117）。这项研究表明，通过分析复杂TME中的多个细胞亚群，有可能识别出仅通过手术切除就可能治愈的患者。
