Journal: Frontier Forum of Clinical Medicine DOI: 10.32629/ffcr.v4i3.21378
Abstract
淋巴毒素β(LTβ)及其受体LTβR构成的信号轴是肿瘤相关炎症和免疫调控的重要通路 ,不仅参与淋巴器官发育和免疫稳态维持,还可以激活经典及非经典NF- κB信号通路调控三级淋巴样结构形成、免疫细胞募集与极化、肿瘤细胞侵袭转移、 血管生成、恶性腹水形成及肿瘤干细胞维持等过程。越来越多研究表明,LTβ/LTβR信 号在卵巢癌肿瘤微环境重塑和疾病进展中发挥关键作用,并具有潜在的治疗靶点价值 。本文综述了LTβ/LTβR信号通路的分子生物学基础及其在卵巢癌中的作用机制,并总 结了相关靶向治疗的研究进展,期望为卵巢癌精准治疗及新型治疗策略开发提供理论 依据。
Keywords
LTβ；卵巢癌；肿瘤微环境；NF-κB；三级淋巴样结构
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[5] Ransmayr B,Bal SK,Thian M,et al.LTβR deficiency causes lymph node aplasia and impaired B-cell differentiation[J].Sci Immunol,2024,9(101):eadq8796.
[6] Sun SC.The non-canonical NF-κB pathway in immunity and inflammation[J].Nat Rev Immunol,2017,17(9):545-558.
[7] Wang L,Fan J,Wu S,et al.LTBR acts as a novel immune checkpoint of tumor-associated macrophages for cancer immunotherapy[J].iMeta,2024,3(5):e233.
[8] Lau TS,Chung TK,Cheung TH,et al.Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts[J].J Pathol,2014,232:43-56.
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[10] Bianchi R,Ganesan A,Chen Y,et al.FAP-targeted LTBR agonist drives HEV differentiation and immune niche formation for improved immunotherapy response in solid tumours[J].Clin Cancer Res,2026.
[11] Harrington BS,Annunziata CM.NF-κB Signaling in Ovarian Cancer[J].Cancers,2019,11(8):1182.
[12] Xu K,Kessler A,Nichetti F,et al.LTβ-activated LTBR/NIK/RELB axis drives proliferation[J].Liver Int,2024,44(11):2950-2963.
[13] Zhang G,Feizi N,Zhao D,Halesha L,Williams AL, Randhawa PS, et al.Lymphotoxin beta receptor and tertiary lymphoid organs shape acute and chronic allograft rejection[J].JCI Insight,2024,9(15):e177555.
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[15] Sun X,Yu J,Cui X,et al.Inhibition of USP21 leads to ovarian carcinoma cell death by suppressing MAPK signaling[J].Biotechnol Appl Biochem,2024,71(1):232-239.
[16] Aoyagi R,Maehara T, Koga R,et al.Single-cell transcriptomics reveals cytotoxic Tfh cells in tertiary lymphoid structures[J].J Allergy Clin Immunol,2024,153(2):513-520.
[17] Bery AI,Shepherd HM,Li W,et al.Role of tertiary lymphoid organs in the regulation of immune responses in the periphery[J].Cell Mol Life Sci,2022,79(7):359.
[18] Filderman JN,Appleman M, Chelvanambi M,et al.STINGing the tumor microenvironment to promote therapeutic tertiary lymphoid structure development[J].Front Immunol,2021,12:690105.
[19] Zheng X,Wang X,Cheng X,et al.Single-cell analyses implicate ascites in remodeling ovarian cancer ecosystems[J].Nat Cancer,2023,4(8):1138-1156.
[20] Zhang M,Bao Y,Zhang H,et al.Intraperitoneal bevacizumab combined with HIPEC in ovarian cancer[J].J Obstet Gynaecol,2023,43(1):204940.
[21] Mei S,Chen X,Wang K,et al.Tumor microenvironment in ovarian cancer peritoneal metastasis[J].Cancer Cell Int,2023,23(1):11.
[22] 王悦,苏荣健,张蕴莉.黄芩素下调NF-κB/Bcl- 2通路诱导卵巢癌Skov3细胞凋亡[J].中国妇产科临床杂志,2023,24(5):460-463.
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[24] Alshehri S, Pavlovič T,Farsinejad S,et al.Extracellular matrix modulates outgrowth dynamics in ovarian cancer[J].Adv Biol,2022,6(12):2200197.
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