ATM kinase regulates tumor immunoreactions in lymphocyte-predominant breast cancer through modulation of NKG2D ligand and TNF cytokines on tumor cells
ATM kinase regulates tumor immunoreactions in lymphocyte-predominant breast cancer through modulation of NKG2D ligand and TNF cytokines on tumor cells
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ATM激酶通过调节肿瘤细胞上的NKG2D配体和TNF细胞因子来调节淋巴细胞为主的乳腺癌中的肿瘤免疫反应
DOI：
10.1007/s00795-020-00247-5
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发表时间：
2020-02-17
影响因子：
1.8
通讯作者：
Guo, Xiaojing
中科院分区：
文献类型：
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作者：
Xu, Peng;Sun, Yuanyuan;Guo, Xiaojing
为了探讨Ataxia毛细血管扩张突变激酶（ATM）对淋巴细胞主导型乳腺癌（LPBC）免疫反应的影响，特别是它在三阴性乳腺癌（TNBC）中的作用，我们对194例LPBC进行了鉴定，并检索了相关的临床资料。采用免疫组织化学方法检测ATM、活化ATM （P-ATM）、Fas配体（FASL）、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、主要组织相容性复合体I类链相关蛋白A （MICA）、CD8、叉头盒P3 （FOXP3）的表达。我们发现ATM在肿瘤细胞上的表达与P-ATM和MICA表达上调（P < 0.05）， FASL和TRAIL表达下调（P < 0.01）， Ki-67肿瘤标记降低相关（P < 0.05）。然而，在TNBC组中，仅发现FASL表达负相关（P = 0.001）。与非TNBC相比，TNBC中ATM和MICA表达显著下调（P < 0.01）， TRAIL表达显著上调（P < 0.01）。TNBC中Tregs升高（P < 0.05）， CD8 + TILs降低（P < 0.01）。TNBC组Ki-67指数高于非TNBC组（P < 0.01）。ATM可能通过上调MICA和下调FASL和TRAIL在LPBC的免疫反应中发挥重要作用。TNBC中下调的ATM表达可能是导致肿瘤免疫活性受损、肿瘤生长迅速和临床病程侵袭性的原因。
To explore impact of Ataxia telangiectasia mutated (ATM) kinase on immunoreactions in lymphocyte-predominant breast cancer (LPBC), particularly its role in triple negative breast cancer (TNBC), 194 cases of LPBC were identified with pertinent clinical information retrieved. The expressions of ATM, activated ATM (P-ATM), Fas ligand (FASL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), major histocompatibility complex class I chain-related protein A (MICA), CD8, and Forkhead box P3 (FOXP3) were assessed by immunohistochemically. We found that ATM expressed on tumor cells was correlated with upregulated expression of P-ATM and MICA (P < 0.05), down-regulated expression of FASL and TRAIL (P < 0.01), and decreased Ki-67 tumor labeling (P < 0.05). However, within the TNBC group, only a negative correlation with FASL expression was found (P = 0.001). ATM and MICA expressions were significantly down -regulated in TNBC (P < 0.01) compared to non-TNBC, while TRAIL was significantly upregulated (P < 0.01). Tregs were increased in TNBC (P < 0.05), with CD8 + TILs decreased (P < 0.01). Ki-67 index was higher in TNBC than in non-TNBC (P < 0.01). ATM may play an important role in immunoreaction of LPBC, probably through upregulation of MICA and down-regulation of FASL and TRAIL. The down-regulated ATM expression in TNBC might be responsible for impaired tumor immunoactivity, rapid tumor growth, and aggressive clinical course.