Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
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DOI：
10.1136/jitc-2019-000169
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发表时间：
2020-01-01
影响因子：
10.9
通讯作者：
Wu, Kejin
中科院分区：
文献类型：
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作者：
Bai, Fang;Zhang, Peng;Wu, Kejin
研究背景调节性T细胞(Treg)在三阴性乳腺癌的抗肿瘤免疫中发挥负作用，因此寻找Treg细胞的潜在治疗靶点具有重要意义。方法首先利用TCGA数据分析乳腺癌患者膜联蛋白A1(ANXA1)的表达和生存情况。采用ELISA法检测恶性和良性乳腺肿瘤患者血浆ANXA1水平。接下来，通过抑制实验研究ANXA1对Treg细胞的影响，并通过RNA测序检测ANXA1如何调节Treg细胞的功能。最后，在 balb/c 小鼠中进行了体内实验，以测试 ANXA1 阻断剂 Boc1 是否可以缩小肿瘤并影响 Treg 细胞的功能。结果我们的数据表明，ANXA1 表达与较低的生存率和较高的乳腺恶性肿瘤风险相关。抑制实验表明ANXA1可以增强Treg细胞的抑制功能。 RNA测序结果表明Boc1可以降低Treg细胞中颗粒酶A mRNA的表达。动物实验表明Boc1可以缩小肿瘤体积并下调Treg细胞功能。结论ANXA1可以增强Treg细胞功能并降低乳腺癌患者的生存率。靶向 ANXA1 可以降低 Treg 细胞功能并缩小乳腺肿瘤。
BackgroundRegulatory T (Treg) cells play a negative role in anti-tumor immunity against triple-negative breast cancer, so it is of great significance to find the potential therapeutic target of Treg cells.MethodsFirst, Annexin A1 (ANXA1) expression and survival of patients with breast cancer were analyzed using TCGA data. Then plasma ANXA1 levels in patients with malignant and benign breast tumors were detected by ELISA. Next, the effect of ANXA1 on Treg cells was studied through suppressive assays, and how ANXA1 regulates the function of Treg cells was detected by RNA sequencing. Finally, the in vivo experiment in balb/c mice was conducted to test whether the ANXA1 blocker Boc1 could shrink tumors and affect the function of Treg cells.ResultsOur data suggest that ANXA1 expression is associated with lower survival and a higher risk of breast malignancy. Suppressive assays show that ANXA1 can enhance the inhibition function of Treg cells. RNA-Sequencing results indicate that Boc1 could reduce the expression of granzyme A mRNA in Treg cells. Animal experiments have been done to show that Boc1 can reduce tumor size and down regulate Treg cell function.ConclusionsANXA1 can enhance the function of Treg cells and reduce the survival rate of patients with breast cancer. Targeting ANXA1 can reduce Treg cell function and shrink breast tumors.