CD16 expression on neutrophils predicts treatment efficacy of capecitabine in colorectal cancer patients
CD16 expression on neutrophils predicts treatment efficacy of capecitabine in colorectal cancer patients
复制标题
中性粒细胞上 CD16 的表达预测结直肠癌患者卡培他滨的治疗效果
DOI：
10.1186/s12865-020-00375-8
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发表时间：
2020-08-08
期刊：
影响因子：
3
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Lu, Yu;Huang, Yizhou;Zhang, Yan
早期发现卡培他滨耐药可以大大提高结直肠癌（CRC）患者的总体生存率。以往的研究表明，检测外周血中的免疫细胞有助于预测化疗的疗效。方法对接受卡培他滨治疗的结直肠癌患者进行外周血免疫学检测。我们分析了卡培他滨耐药患者的异常免疫细胞群与主要临床特征之间的关系。此外，使用该群体进行RNA测序、细胞表面标志物表达的分析以及与其他主要免疫细胞群体的相关性，以探索这些细胞的可能功能。结果卡培他滨耐药的结直肠癌患者中性粒细胞表面CD16表达水平下调。卡培他滨治疗后CD16（低/-）中性粒细胞的患者有不良的临床特征。更重要的是，中性粒细胞表面CD16表达水平的变化比CT扫描早得多。RNA测序结果显示，与卡培他滨敏感患者的CD16（+）中性粒细胞相比，卡培他滨耐药患者的CD16（低/-）中性粒细胞具有较低的嗜中性粒细胞相关基因表达水平，提示该CD16（低/-）群体可能是未成熟的中性粒细胞。卡培他滨治疗后中性粒细胞表面CD16的表达水平与CD8 + T细胞、CD4 + T细胞、NK细胞和单核细胞等抗肿瘤免疫细胞亚群的数量呈正相关。结论外周血中性粒细胞CD16表达水平是预测卡培他滨治疗结直肠癌疗效的良好指标。
Background Early detection of capecitabine-resistance could largely increase overall survival of colorectal cancer (CRC) patients. Previous studies suggested examination of immune cells in peripheral blood would help to predict efficacy of chemotherapy. Methods We examined the immunological characteristics of peripheral blood in CRC patients with capecitabine treatment. We analyzed the relationships between the abnormal immune cell population in capecitabine-resistance patients and major clinical features. Furthermore, RNA sequencing, analyses of cell surface marker expression and the correlations with other major immune cell populations were performed using this population to explore the possible function of these cells. Results The expression level of CD16 on neutrophils was down-regulated in capecitabine-resistant CRC patients. Patients with CD16(low/-)neutrophils after capecitabine therapy had adverse clinical features. What's important, the change of CD16 expression level on neutrophils appeared much earlier than CT scan. RNA sequencing revealed that CD16(low/-)neutrophils in capecitabine-resistant patients had lower expression level of neutrophil-related genes, compared to CD16(+)neutrophils in capecitabine-sensitive patients, suggesting this CD16(low/-)population might be immature neutrophils. Furthermore, the expression level of CD16 on neutrophils in patients with capecitabine treatment was positively correlated with the number of anti-tumor immune cell subsets, such as CD8(+)T cell, CD4(+)T cell, NK cell and monocyte. Conclusions Our findings indicated that CD16 expression on neutrophils in peripheral blood was a good prognostic marker for predicting efficacy of capecitabine in CRC patients.