Decreased STING predicts adverse efficacy in bortezomib regimens and poor survival in multiple myeloma.

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Yang Liu, Yu Zhao, Bo Li, Xiaomin Chen, Hao Xiong, Chunlan Huang
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引用次数: 0

Abstract

Purpose: STING (stimulator of interferon genes) is involved in viral and bacterial defense through interferon pathway and innate immunity. Increased susceptibility to infection is a common manifestation of multiple myeloma (MM). Thus, we aimed to explore the clinical significance and possible mechanism of STING in MM.

Materials and methods: Immunohistochemistry and qPCR were used to detect STING expression in the bone marrow of MM patients, and flow cytometry was used to detect the amount of intracellular STING. All data were analyzed with clinical characteristics.

Results: STING expression was remarkably reduced in MM tissues compared to normal tissues and was not associated with stage. Multivariate analysis identified STING as an independent prognostic factor in MM patients (P = 0.001). In the bortezomib-containing regimens, patients with low STING expression were more difficult to achieve remission. A model incorporating STING and m-SMART significantly improved the predictive accuracy of overall survival in bortezomib regimens (AUC, 0.511 to 0.630, P = 0.044). Bortezomib efficacy has been reported to correlate with activated immunity, but the low expression group manifested as immune apathy. Although baseline characteristics showed intergroup differences in infection, the low expression group had an increased proportion of bacterial infections (1.7-fold) and a prolonged duration of antibiotic/antifungal medication (3.55 additional days); these patients were accompanied by a decreased neutrophil-to-lymphocyte ratio (NLR) and rarely activated neutrophils and leukocytes. The intracellular STING ratio was also defective in neutrophil-dominated leukocytes.

Conclusion: Our study revealed that STING had a strong association with bortezomib and could serve as a potential target for immunotherapy in multiple myeloma.

降低STING预示着硼替佐米方案的不良疗效和多发性骨髓瘤患者的不良生存率。
目的:干扰素基因刺激因子STING (stimulator of interferon genes)通过干扰素通路和先天免疫参与病毒和细菌防御。对感染的易感性增加是多发性骨髓瘤(MM)的常见表现。因此,我们旨在探讨STING在MM中的临床意义和可能的机制。材料和方法:采用免疫组织化学和qPCR检测MM患者骨髓中STING的表达,流式细胞术检测细胞内STING的量。对所有资料进行临床特征分析。结果:与正常组织相比,MM组织中STING的表达明显降低,且与分期无关。多变量分析发现STING是MM患者的独立预后因素(P = 0.001)。在含有硼替佐米的方案中,低STING表达的患者更难以达到缓解。结合STING和m-SMART的模型显著提高了硼替佐米方案总生存期的预测准确性(AUC, 0.511至0.630,P = 0.044)。据报道,硼替佐米的疗效与激活免疫有关,但低表达组表现为免疫冷漠。尽管基线特征显示了感染的组间差异,但低表达组的细菌感染比例增加(1.7倍),抗生素/抗真菌药物治疗持续时间延长(额外3.55天);这些患者伴有中性粒细胞与淋巴细胞比率(NLR)下降,中性粒细胞和白细胞很少活化。在中性粒细胞占主导的白细胞中,细胞内STING比例也存在缺陷。结论:我们的研究表明,STING与硼替佐米有很强的相关性,可以作为多发性骨髓瘤免疫治疗的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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