Annexin A3 upregulates the infiltrated neutrophil-lymphocyte ratio to remodel the immune microenvironment in hepatocellular carcinoma.
Annexin A3 upregulates the infiltrated neutrophil-lymphocyte ratio to remodel the immune microenvironment in hepatocellular carcinoma.
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膜联蛋白 A3 上调浸润性中性粒细胞-淋巴细胞比率，重塑肝细胞癌的免疫微环境。
DOI：
10.1016/j.intimp.2020.107139
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发表时间：
2020-11
影响因子：
5.6
通讯作者：
Xia Jian-Chuan
中科院分区：
文献类型：
--
作者：
Zhu Qian;Pan Qiu-Zhong;Zhong Ai-Lin;Hu Hao;Zhao Jing-Jing;Tang Yan;Hu Wan-Ming;Li Min;Weng De-Sheng;Chen Ming-Yuan;Ma Gang;Xia Jian-Chuan
越来越多的证据表明，肝细胞癌（HCC）的发生和发展需要炎症反应。具有高度相似结构的膜联蛋白家族蛋白已被证明参与肿瘤发展中的促炎或抗炎调节。然而，ANXA 3在HCC免疫微环境中的潜在作用仍然未知。在本研究中，我们发现ANXA 3表达增加与HCC中较高的浸润嗜中性淋巴细胞-淋巴细胞比率（iNLR）相关。此外，具有高iNLR和高ANXA 3表达的HCC患者具有最高的死亡风险。ANXA 3可以在细胞裂解物和培养上清液中检测到。然而，分泌型ANXA 3不直接调节iNLR。进一步的研究表明，ANXA 3通过诱导HCC细胞释放趋化因子CXCL 8和CCL 25上调iNLR。我们进一步证实了ANXA 3促进肿瘤发生，并在体内检测到ANXA 3与iNLR或趋化因子之间的相同关联。我们的研究结果表明，ANXA 3调节趋化因子重塑iNLR并促进HCC的致瘤性。这些结果进一步扩展了我们对ANXA 3在HCC微环境中的理解，并可能为HCC患者的分子治疗研究提供新的靶点。
Accumulating evidence has indicated that inflammation is required for the initiation and progression of hepatocellular carcinoma (HCC). The annexin family protein, which has a highly similar structure, has been demonstrated to participate in pro- or anti-inflammatory regulation in the developing of tumours. However, the potential effects of ANXA3 in the immune microenvironment of HCC remain unknown. In present study, we found that increased ANXA3 expression is associated with a higher infiltrated neutrophil-lymphocyte ratio (iNLR) in HCC. Moreover, HCC patients with a high iNLR and high ANXA3 expression confer the highest risk of death. ANXA3 can be detected in both cell lysates and culture supernatants. However, the secretory ANXA3 did not directly regulate the iNLR. Further study demonstrated that ANXA3 upregulated the iNLR by inducing chemokine CXCL8 and CCL25 release from HCC cells. We further confirmed that ANXA3 promotes tumourigenesis and detected the same associations between ANXA3 and the iNLR or chemokinesin vivo. Our findings indicate that ANXA3 regulates the chemokine to remodel the iNLR and promotes tumourigenicity in HCC. These results further expanded our understanding of ANXA3 in the microenvironment of HCC and might provide novel targets for the investigation of molecular treatments for HCC patients.
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