Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Machine Learning Group, Technical University Berlin, Berlin, Germany; Department of Brain and Cognitive Engineering, Korea University, 145 Anam-ro, Seongbuk- gu, Seoul 136-713, South Korea; Max-Planck-Institute for Informatics, Saarbrücken, Germany.
Semin Cancer Biol. 2018 Oct;52(Pt 2):151-157. doi: 10.1016/j.semcancer.2018.07.001. Epub 2018 Jul 7.
The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.
肿瘤浸润淋巴细胞 (TILs) 的程度,以及免疫调节配体、肿瘤突变负担和其他生物标志物,已被证明是几种癌症对免疫检查点治疗反应的标志物。因此,病理学家已经开始设计标准化的视觉方法来量化 TILs 以进行治疗预测。然而,尽管已经进行了成功的标准化努力,但视觉 TIL 估计仍然缓慢,精度有限,并且缺乏评估更复杂特性(如 TIL 分布模式)的能力。因此,需要计算图像分析方法来提供标准化和高效的 TIL 量化。在这里,我们讨论了不同的自动 TIL 评分方法,范围从经典的图像分割开始,其中识别细胞边界,并根据形状特性对生成的对象进行分类,到基于机器学习的方法,这些方法无需分割即可直接对细胞进行分类,但依赖于大量的训练数据。与经常因其“黑盒”特性而受到批评的传统机器学习 (ML) 方法相反,我们还讨论了可解释的机器学习。此类方法使 ML 结果具有可解释性,并通过高分辨率热图解释计算决策过程,从而允许在生物医学研究和诊断中进行量化和可信度检查。
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