Zhang Chenyue, Wang Hui, Wang Xia, Zhao Chenglong, Wang Haiyong
Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, 200032, China.
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, PR China.
Cancer Cell Int. 2020 Dec 7;20(1):583. doi: 10.1186/s12935-020-01671-4.
PD-L1 inhibitors is widely applied in lung adenocarcinoma patients. Tumor cells with high PD-L1 expression could trigger immune evasion. Cancer stem cells (CSCs) can evade from immunesurveillance due to their immunomodulating effects. However, the correlation between CSC and PD-L1 and some immune-related markers is seldom reported in patients with lung adenocarcinoma. Therefore, we aimed to ascertain their association in lung adenocarcinoma patients.
We assessed CD44 expression and its association with PD-L1 in lung adenocarcinoma, using Tumor Immune Estimation Resource (TIMER), which was further validated in our patient cohort. The immune cells infiltration was depicted by CIBERSORT using GEO database. The correlation between CD44 and immune cells was also analyzed. We further evaluated the prognostic role of CD44 in patients with lung adenocarcinoma both using Kaplan-Meier plotter and validated in our patient cohort.
Positive association between CD44 and PD-L1 were found in lung adenocarcinoma patients. T cells CD4 memory resting cells and mast cells resting cells varied significantly between patients with CD44 high and those with CD44 low. Furthermore, positive association could be found between CD44 expression and immune cells. Arm-level depletion of CD44 was linked with B cell, CD4 T cell, neutrophil and dendritic cell infiltration. Patients with higher CD44 levels had worsened overall survival (OS).
In summary, these results demonstrate that CD44 was associated with PD-L1 and infiltration of immune cells, and was a negative prognostic factor for predicting worsened OS in lung adenocarcinoma.
程序性死亡受体配体1（PD-L1）抑制剂广泛应用于肺腺癌患者。高表达PD-L1的肿瘤细胞可引发免疫逃逸。癌症干细胞（CSCs）因其免疫调节作用可逃避免疫监视。然而，在肺腺癌患者中，癌症干细胞与PD-L1及一些免疫相关标志物之间的相关性鲜有报道。因此，我们旨在确定它们在肺腺癌患者中的关联。
我们使用肿瘤免疫评估资源（TIMER）评估肺腺癌中CD44的表达及其与PD-L1的关联，并在我们的患者队列中进一步验证。使用基因表达综合数据库（GEO）通过CIBERSORT描绘免疫细胞浸润情况。还分析了CD44与免疫细胞之间的相关性。我们进一步使用Kaplan-Meier生存曲线分析软件评估CD44在肺腺癌患者中的预后作用，并在我们的患者队列中进行验证。
在肺腺癌患者中发现CD44与PD-L1呈正相关。CD44高表达患者和CD44低表达患者之间，CD4记忆静止T细胞和静止肥大细胞有显著差异。此外，CD44表达与免疫细胞之间呈正相关。CD44的基因水平缺失与B细胞、CD4 T细胞、中性粒细胞和树突状细胞浸润有关。CD44水平较高的患者总生存期（OS）较差。
总之，这些结果表明，CD44与PD-L1及免疫细胞浸润相关，是预测肺腺癌患者总生存期恶化的不良预后因素。
