DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer.
DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer.
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基于 DNA 甲基化的 CD8 肿瘤浸润淋巴细胞特征能够评估结直肠癌的免疫反应和预后。
DOI：
10.1136/jitc-2021-002671
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发表时间：
2021-09
影响因子：
10.9
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Zou Q;Wang X;Ren D;Hu B;Tang G;Zhang Y;Huang M;Pai RK;Buchanan DD;Win AK;Newcomb PA;Grady WM;Yu H;Luo Y
肿瘤浸润淋巴细胞（TIL），特别是CD 8 + TIL，可用于预测免疫治疗反应性和生存结果。然而，CD 8 + TIL的评价目前依赖于具有高变异性的组织病理学方法。因此，我们的目标是开发一种CD 8 + TIL（CD 8 + MeTIL）的DNA甲基化特征，可以评估结直肠癌（CRC）的免疫反应和预后。通过使用从Illumina EPIC甲基化阵列鉴定的CD 8 + T细胞特异性差异甲基化位置（DMP）构建CD 8 + MeTIL特征评分。使用免疫细胞、结肠上皮细胞和两个CRC群组（n=282和335）来开发基于PCR的测定，用于以单碱基分辨率（QASM）定量分析DNA甲基化，以确定CD 8 + MeTIL特征评分。鉴定了三种CD 8 + T细胞特异性DMP以构建CD 8 + MeTIL特征评分，其显示了CD 8 + T细胞和其他细胞之间的显著区分性。我们开发的用于CD 8 + MeTIL标志物的QASM测定法可以以完全定量、准确和简单的方式测量CD 8 + TIL分布。通过QASM测定确定的CD 8 + MeTIL评分显示与基于组织病理学的CD 8 + TIL计数和基于基因表达的免疫标记物强相关。此外，低CD 8 + MeTIL评分（富集的CD 8 + TIL）与MSI-H肿瘤相关，并预测CRC队列的生存率更高。本研究开发了一种基于DNA甲基化的定量标记，可可靠地评估CRC中的CD 8 + TIL和预后。这种方法有可能成为研究CD 8 + TIL的工具和治疗方法（包括免疫治疗）的生物标志物。
Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC). A CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score. Three CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts. This study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.
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影响因子：
11.1
作者：
Hu X;Li YQ;Li QG;Ma YL;Peng JJ;Cai SJ
通讯作者：
Cai SJ
全基因组分析识别结直肠癌中 NTRKs 基因内的关键 DNA 甲基化。
影响因子：
7.4
作者：
Chen Z;Huang Z;Luo Y;Zou Q;Bai L;Tang G;Wang X;Cao G;Huang M;Xiang J;Yu H
通讯作者：
Yu H
影响因子：
15.9
作者：
Jeschke, Jana;Bizet, Martin;Fuks, Francois
通讯作者：
Fuks, Francois
影响因子：
7.7
作者：
Jenkins, Mark A.;Win, Aung Ko;Haile, Robert W.
通讯作者：
Haile, Robert W.
影响因子：
11.5
作者：
Governa, Valeria;Trella, Emanuele;Spagnoli, Giulio C.
通讯作者：
Spagnoli, Giulio C.