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自然杀伤细胞中CS1表达模式及浆细胞发育异常中的相关因素:对埃罗妥珠单抗治疗和嵌合抗原受体T细胞疗效的影响。

CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy.

作者信息

Li Chunhui, Wang Di, Xu Yanjie, Mao Xia, Que Yimei, Li Zhe, Yu Qiuxia, Xu Menglei, An Ning, Long Xiaolu, Li Chunrui

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei 430030, China.

出版信息

J Cancer. 2024 Apr 8;15(10):3065-3075. doi: 10.7150/jca.93637. eCollection 2024.

Abstract

Treatment with elotuzumab alone has no discernible antitumor effect and progress in chimeric antigen receptor T cells (CAR-T) therapy targeting CS1 is relatively slow. A retrospective analysis was performed on 236 patients with multiple myeloma (MM) and 30 patients with other plasma cell dyscrasias (PCDs). CS1 expression in NK cells, lymphocytes, and monoclonal plasma cells was assessed using multiparameter flow cytometry. Furthermore, new explorations were undertaken regarding the antitumor applications of elotuzumab. Patients with MM had significantly higher CS1 expression levels in plasma cells than other patients with PCDs, with no significant differences between lymphocytes and NK cells. In both patients with MM and other PCDs, CS1 expression was significantly higher in plasma cells than in NK cells and lymphocytes. Univariate and multivariate analyses revealed a significant correlation between CS1 expression in plasma (r = 0.60; P < 0.001) and NK (r = 0.79; P < 0.001) cells. Factors such as cytogenetic abnormalities, disease progression, and survival were not associated with CS1 expression in NK cells. Moreover, this study showed that elotuzumab strongly increases the cytotoxicity of NK cells against non-plasma and plasma tumor cells independent of their CS1 expression level. This underscores the potential of elotuzumab in combination with NK cells as an effective therapeutic strategy against a broad spectrum of tumor types.

摘要

单独使用埃罗妥珠单抗治疗没有明显的抗肿瘤效果,并且针对CS1的嵌合抗原受体T细胞(CAR-T)疗法进展相对缓慢。对236例多发性骨髓瘤(MM)患者和30例其他浆细胞异常(PCD)患者进行了回顾性分析。使用多参数流式细胞术评估NK细胞、淋巴细胞和单克隆浆细胞中CS1的表达。此外,还对埃罗妥珠单抗的抗肿瘤应用进行了新的探索。MM患者浆细胞中的CS1表达水平明显高于其他PCD患者,淋巴细胞和NK细胞之间无显著差异。在MM患者和其他PCD患者中,浆细胞中的CS1表达均明显高于NK细胞和淋巴细胞。单因素和多因素分析显示,血浆(r = 0.60;P < 0.001)和NK细胞(r = 0.79;P < 0.001)中CS1的表达之间存在显著相关性。细胞遗传学异常、疾病进展和生存等因素与NK细胞中CS1的表达无关。此外,本研究表明,埃罗妥珠单抗可强烈增强NK细胞对非浆细胞和浆细胞肿瘤细胞的细胞毒性,而与它们的CS1表达水平无关。这突出了埃罗妥珠单抗与NK细胞联合作为针对广泛肿瘤类型的有效治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a413/11064268/eba795b03291/jcav15p3065g001.jpg

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