Sabrina Saima, Takeda Yuji, Kato Tomoyuki, Naito Sei, Ito Hiromi, Takai Yuki, Ushijima Masaki, Narisawa Takafumi, Kanno Hidenori, Sakurai Toshihiko, Saitoh Shinichi, Araki Akemi, Tsuchiya Norihiko, Asao Hironobu
Department of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
Department of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
Biomedicines. 2023 Apr 27;11(5):1296. doi: 10.3390/biomedicines11051296.
The therapeutic outcome of immune checkpoint inhibition (ICI) can be improved through combination treatments with ICI therapy. Myeloid-derived suppressor cells (MDSCs) strongly suppress tumor immunity. MDSCs are a heterogeneous cell population, originating from the unusual differentiation of neutrophils/monocytes induced by environmental factors such as inflammation. The myeloid cell population consists of an indistinguishable mixture of various types of MDSCs and activated neutrophils/monocytes. In this study, we investigated whether the clinical outcomes of ICI therapy could be predicted by estimating the status of the myeloid cells, including MDSCs. Several MDSC indexes, such as glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80), CD16, and latency-associated peptide-1 (LAP-1; transforming growth factor-β1 precursor), were analyzed via flow cytometry using peripheral blood derived from patients with advanced renal cell carcinoma ( = 51) immediately before and during the therapy. Elevated CD16 and LAP-1 expressions after the first treatment were associated with a poor response to ICI therapy. Immediately before ICI therapy, GPI-80 expression in neutrophils was significantly higher in patients with a complete response than in those with disease progression. This is the first study to demonstrate a relationship between the status of the myeloid cells during the initial phase of ICI therapy and clinical outcomes.
通过免疫检查点抑制剂(ICI)疗法与其他疗法联合使用,可以改善ICI的治疗效果。髓源性抑制细胞(MDSC)可强烈抑制肿瘤免疫。MDSC是一种异质性细胞群体,源于由炎症等环境因素诱导的中性粒细胞/单核细胞的异常分化。髓样细胞群体由各种类型的MDSC与活化的中性粒细胞/单核细胞组成的难以区分的混合物。在本研究中,我们调查了通过评估包括MDSC在内的髓样细胞状态是否可以预测ICI疗法的临床结果。使用晚期肾细胞癌患者(n = 51)治疗前及治疗期间的外周血,通过流式细胞术分析了几种MDSC指标,如糖基磷脂酰肌醇锚定80 kD蛋白(GPI-80)、CD16和潜伏相关肽-1(LAP-1;转化生长因子-β1前体)。首次治疗后CD16和LAP-1表达升高与ICI疗法反应不佳相关。在ICI治疗前,完全缓解患者中性粒细胞中的GPI-80表达显著高于疾病进展患者。这是第一项证明ICI治疗初始阶段髓样细胞状态与临床结果之间关系的研究。