Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
J Mol Diagn. 2020 May;22(5):685-698. doi: 10.1016/j.jmoldx.2020.02.008. Epub 2020 Mar 13.
To understand the immune landscape of deficient mismatch repair colorectal cancer (dMMR CRC) tumor microenvironment, gene expression profiling was performed by the nCounter PanCancer Immune Profiling Panel. This study was conducted retrospectively on 89 dMMR-CRC samples. The expression of CD3, CD8, programmed death-1, and programmed death ligand-1 protein was evaluated on a subset of samples by immunohistochemistry, and lymphocyte density was calculated. A subset of deregulated genes was identified. Functional clustering analysis performed on these genes generated four main factors: antigen processing and presentation, with its major histocompatibility complex-II-related genes; genes correlated with the cytotoxic activity of immune system; T-cell chemotaxis/cell adhesion genes; and T-CD4 regulator cell-related genes. A deregulation score (DS) was calculated for each sample. On the basis of their DS, tumors were then classified as COLD (DS ≤ -3) to select the samples with a strong down-regulation of the immune system and NOT COLD (DS ≥ -2). The COLD group of patients showed a worse prognosis in terms of survival considering all patients (P = 0.0172) and patients with metastatic disease (P = 0.0031). These results confirm that dMMR-CRCs do not constitute a homogeneous group as concerns the immune system activity of tumor microenvironment. In particular, the distinction between COLD and NOT COLD tumors may improve the management of these two subsets of patients.
为了了解错配修复缺陷型结直肠癌（dMMR CRC）肿瘤微环境的免疫景观，我们使用 nCounter PanCancer 免疫分析面板对 89 例 dMMR-CRC 样本进行了基因表达谱分析。本研究对 89 例 dMMR-CRC 样本进行了回顾性分析。通过免疫组织化学法评估了部分样本中 CD3、CD8、程序性死亡受体-1（PD-1）和程序性死亡配体-1（PD-L1）蛋白的表达情况，并计算了淋巴细胞密度。鉴定了一组失调基因。对这些基因进行功能聚类分析，生成了四个主要因子：抗原加工和呈递，其主要组织相容性复合体 II 相关基因；与免疫系统细胞毒性活性相关的基因；T 细胞趋化/细胞黏附基因；以及 T-CD4 调节细胞相关基因。为每个样本计算了一个失调评分（DS）。然后根据他们的 DS，将肿瘤分为 COLD（DS≤-3），以选择免疫系统强烈下调的样本，而不是 COLD（DS≥-2）。考虑到所有患者（P=0.0172）和转移性疾病患者（P=0.0031），COLD 组患者的预后更差。这些结果证实，dMMR-CRC 在肿瘤微环境的免疫系统活性方面并不构成一个同质的群体。特别是，COLD 和 NOT COLD 肿瘤之间的区别可能会改善这两组患者的治疗管理。
