Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling
Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling
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DOI：
10.18632/oncotarget.8798
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发表时间：
2016-05-24
期刊：
影响因子：
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通讯作者：
Gong, Gyungyub
中科院分区：
文献类型：
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作者：
Lee, Hee Jin;Song, In Hye;Gong, Gyungyub
三阴性乳腺癌（TNBC）中的肿瘤浸润淋巴细胞（TIL）具有很强的预后和预测意义。然而，TNBC中TIL流入的机制尚不清楚。肿瘤细胞上主要组织相容性复合物I类（MHC I）的表达是细胞毒性TIL有效杀伤肿瘤所必需的。在我们目前的研究中，人类白细胞抗原（HLA）的表达与雌激素受体（ER）的表达在正常和癌性乳腺组织呈负相关，与TIL在乳腺癌呈正相关。乳腺癌中ER评分与TIL呈负相关。在癌症基因组图谱（TCGA）数据中，HLA-A和CD 8B基因表达与ESR 1呈负相关，与干扰素相关基因表达呈正相关。癌细胞系百科全书（CCLE）数据也证实了ESR 1和HLA之间的负相关性和干扰素相关和HLA基因表达之间的正相关性。综上所述，我们的数据表明，HLA在腔型肿瘤中的低表达可能与这些肿瘤中的低水平TIL相关。进一步研究TNBC中较高的HLA表达和TIL内流的机制可能有助于增强宿主的免疫应答。
Tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) have a strong prognostic and predictive significance. However, the mechanism of TIL influx in TNBC is unclear. Expression of major histocompatibility complex class I (MHC I) on the tumor cell is essential for the effective killing of tumor by cytotoxic TILs. In our current study, human leukocyte antigen (HLA) expression was inversely correlated with estrogen receptor (ER) expression in normal and cancerous breast tissue and positively correlated with TILs in breast cancer. The ER score was inversely correlated with TILs in breast cancer. HLA-A and CD8B gene expression was negatively correlated with ESR1 and positively correlated with interferon-associated gene expression in The Cancer Genome Atlas (TCGA) data. Negative correlation between ESR1 and HLA and positive correlation between interferon-associated and HLA gene expression were also confirmed in Cancer Cell Line Encyclopedia (CCLE) data. Taken together, our data suggest that a lower expression of HLA in luminal-type tumors might be associated with low level of TILs in those tumors. Further investigation of the mechanism of higher HLA expression and TIL influx in TNBC may help to boost the host immune response.