ANXA3-Rich Exosomes Derived from Tumor-Associated Macrophages Regulate Ferroptosis and Lymphatic Metastasis of Laryngeal Squamous Cell Carcinoma.

IF 8.1 1区 医学 Q1 IMMUNOLOGY
Licheng Xu, Wenjing Li, Danxi Liu, Jing Cao, Jingchun Ge, Xinyu Liu, Yue Wang, Yujian Teng, Pengyan Liu, Xinyue Guo, Chen He, Ming Liu, Linli Tian
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引用次数: 0

Abstract

Tumor-associated macrophages (TAM) induce immunosuppression in laryngeal squamous cell carcinoma (LSCC). The interaction between LSCC cells and TAMs affects the progression of laryngeal cancer through exosomes, but the underlying molecular mechanism remains unclear. Proteomics analysis of TAMs isolated from human laryngeal tumor tissues obtained from patients with confirmed lymphatic metastasis revealed an upregulation of annexin A3 (ANXA3). In TAMs, ANXA3 promoted macrophages to polarize to an M2-like phenotype by activating the AKT-GSK3β-β-catenin pathway. In addition, ANXA3-rich exosomes derived from TAMs inhibited ferroptosis in laryngeal cancer cells through an ATF2-CHAC1 axis, and this process was associated with lymphatic metastasis. Mechanistically, ANXA3 in exosomes inhibited the ubiquitination of ATF2, whereas ATF2 acted as a transcription factor to regulate the expression of CHAC1, thus inhibiting ferroptosis in LSCC cells. These data indicate that abnormal ANXA3 expression can drive TAM reprogramming and promote an immunosuppressive microenvironment in LSCC. Meanwhile, ANXA3-rich exosomes inhibit ferroptosis of LSCC cells and promote lymphatic metastasis, thus promoting tumor progression.

源自肿瘤相关巨噬细胞的富含ANXA3的外泌体可调控喉鳞状细胞癌的铁凋亡和淋巴转移。
肿瘤相关巨噬细胞(TAMs)会诱导喉鳞状细胞癌(LSCC)的免疫抑制。LSCC细胞与TAMs之间的相互作用通过外泌体影响喉癌的进展,但其潜在的分子机制仍不清楚。对从确诊淋巴转移患者的人喉肿瘤组织中分离出的TAMs进行蛋白质组学分析后发现,annexin A3(ANXA3)上调。在TAMs中,ANXA3通过激活AKT-GSK3β-β-catenin通路促进巨噬细胞极化为M2样表型。此外,来自TAMs的富含ANXA3的外泌体通过ATF2-CHAC1轴抑制喉癌细胞的铁突变,这一过程与淋巴转移有关。从机理上讲,外泌体中的ANXA3抑制了ATF2的泛素化,而ATF2则作为转录因子调控CHAC1的表达,从而抑制了LSCC细胞的铁突变。这些数据表明,ANXA3的异常表达可驱动TAM重编程,并促进LSCC中免疫抑制微环境的形成。同时,富含ANXA3的外泌体可抑制LSCC细胞的铁凋亡,促进淋巴转移,从而推动肿瘤进展。
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来源期刊
Cancer immunology research
Cancer immunology research ONCOLOGY-IMMUNOLOGY
CiteScore
15.60
自引率
1.00%
发文量
260
期刊介绍: Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes. Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.
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