泛癌种中 HLA 基因表达与癌症预后和免疫治疗疗效的关联。
Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy.
机构信息
Department of Molecular and Systems Biology, Dartmouth College, Hanover, NH, USA.
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
出版信息
Br J Cancer. 2021 Aug;125(3):422-432. doi: 10.1038/s41416-021-01400-2. Epub 2021 May 12.
BACKGROUND
The function of major histocompatibility complex (MHC) molecules is to bind peptide fragments derived from genomic mutations or pathogens and display them on the cell surface for recognition by cognate T cells to initiate an immune response.
METHODS
In this study, we provide a comprehensive investigation of HLA gene expression in a pan-cancer manner involving 33 cancer types. We utilised gene expression data from several databases and immune checkpoint blockade-treated patient cohorts.
RESULTS
We show that MHC expression varies strongly among cancer types and is associated with several genomic and immunological features. While immune cell infiltration was generally higher in tumours with higher HLA gene expression, CD4+ T cells showed significantly different correlations among cancer types, separating them into two clusters. Furthermore, we show that increased HLA gene expression is associated with prolonged survival in the majority of cancer types. Lastly, HLA gene expression is associated with patient response to immune checkpoint blockade, which is especially prominent for HLA class II expression in tumour biopsies taken during treatment.
CONCLUSION
We show that HLA gene expression is an important feature of tumour biology that has significant impact on patient prognosis.
背景
主要组织相容性复合体（MHC）分子的功能是结合来自基因组突变或病原体的肽片段，并将其呈现在细胞表面，以便同源 T 细胞识别，从而引发免疫反应。
方法
本研究以泛癌的方式对 HLA 基因表达进行了全面研究，涉及 33 种癌症类型。我们利用了来自多个数据库和免疫检查点阻断治疗患者队列的基因表达数据。
结果
我们表明，MHC 表达在癌症类型之间差异很大，与多种基因组和免疫学特征相关。虽然免疫细胞浸润在 HLA 基因表达较高的肿瘤中通常更高，但 CD4+T 细胞在癌症类型之间表现出明显不同的相关性，将它们分为两个簇。此外，我们表明，HLA 基因表达的增加与大多数癌症类型的生存延长相关。最后，HLA 基因表达与患者对免疫检查点阻断的反应相关，这在治疗期间取自肿瘤活检的 HLA Ⅱ类表达中尤为明显。
结论
我们表明，HLA 基因表达是肿瘤生物学的一个重要特征，对患者预后有重大影响。
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