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CD8 T Cell Score as a Prognostic Biomarker for Triple Negative Breast Cancer

机译:CD8 T细胞评分作为三重阴性乳腺癌的预后生物标志物

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CD8 T cell is an essential component of tumor-infiltrating lymphocytes (TIL) and tumor immune microenvironment (TIME). Using the xCell CD8 T cell score of whole tumor gene expression data, we estimated these cells in total of 3837 breast cancer patients from TCGA, METABRIC and various GEO cohorts. The CD8 score correlated strongly with expression of CD8 genes. The score was highest for triple-negative breast cancer (TNBC), and a high score was associated with high tumor immune cytolytic activity and better survival in TNBC but not other breast cancer subtypes. In TNBC, tumors with a high CD8 score had enriched expression of interferon ( IFN )-α and IFN -γ response and allograft rejection gene sets, and greater infiltration of anti-cancerous immune cells. The score strongly correlated with CD4 memory T cells in TNBC, and tumors with both a high CD8 score and high CD4 memory T cell abundance had significantly better survival. Finally, a high CD8 score was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, a high CD8 T cell score is associated with better survival in TNBC, particularly when tumor CD4 memory T cells were elevated. Our findings also suggest a possible use of the score as a predictive biomarker for response to immune checkpoint therapy.
机译:CD8 T细胞是肿瘤浸润淋巴细胞(TIL)和肿瘤免疫微环境(时间)的基本组分。使用全肿瘤基因表达数据的Xcell CD8 T细胞评分,我们估计了来自TCGA,元质量和各种地理群体的3837名乳腺癌患者的这些细胞。 CD8得分强烈地与CD8基因表达强烈相关。对于三阴性乳腺癌(TNBC)的分数最高,并且高分与高肿瘤免疫细胞溶解活性相关,并且在TNBC中更好地存活但不是其他乳腺癌亚型。在TNBC中,具有高CD8评分的肿瘤富集了干扰素(IFN)-α和IFN-γ响应和同种异体移植排斥基因集的表达,以及更大的抗癌症免疫细胞渗透。与TNBC中的CD4内存T细胞强烈相关的分数,以及具有高CD8评分和高CD4内存T细胞丰度的肿瘤具有显着更好的存活率。最后,高CD8得分与多种免疫检查点分子的高表达显着相关。总之,高CD8 T细胞评分与TNBC的更好存活相关,特别是当肿瘤CD4内存T细胞升高时。我们的调查结果还建议使用分数作为预测生物标志物,以应对免疫检查点治疗。

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