Liu Yang, Zhao Yu, Li Bo, Chen Xiaomin, Xiong Hao, Huang Chunlan
Stem Cell Immunity and Regeneration Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China.
Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
Clin Exp Med. 2025 Jan 14;25(1):37. doi: 10.1007/s10238-025-01561-x.
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.
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.
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.
Our study revealed that STING had a strong association with bortezomib and could serve as a potential target for immunotherapy in multiple myeloma.
干扰素基因刺激因子（STING）通过干扰素途径和固有免疫参与病毒和细菌防御。感染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中的临床意义及可能机制。
采用免疫组织化学和qPCR检测MM患者骨髓中STING表达，采用流式细胞术检测细胞内STING含量。所有数据均与临床特征进行分析。
与正常组织相比，MM组织中STING表达显著降低，且与分期无关。多因素分析确定STING为MM患者的独立预后因素（P = 0.001）。在含硼替佐米的治疗方案中，STING低表达患者更难实现缓解。包含STING和m-SMART的模型显著提高了硼替佐米治疗方案中总生存的预测准确性（AUC，0.511至0.630，P = 0.044）。据报道硼替佐米疗效与激活的免疫相关，但低表达组表现为免疫无反应。虽然基线特征显示组间在感染方面存在差异，但低表达组细菌感染比例增加（1.7倍），抗生素/抗真菌药物使用时间延长（额外3.55天）；这些患者伴有中性粒细胞与淋巴细胞比值（NLR）降低，中性粒细胞和白细胞很少被激活。在以中性粒细胞为主的白细胞中，细胞内STING比例也存在缺陷。
我们的研究表明，STING与硼替佐米密切相关，可作为多发性骨髓瘤免疫治疗的潜在靶点。
