CD44, a marker of cancer stem cells, is positively correlated with PD-L1 expression and immune cells infiltration in lun
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Cancer Cell International Open Access
PRIMARY RESEARCH
CD44, a marker of cancer stem cells, is positively correlated with PD‑L1 expression and immune cells infiltration in lung adenocarcinoma Chenyue Zhang1†, Hui Wang2†, Xia Wang3, Chenglong Zhao4 and Haiyong Wang3*
Abstract Background: 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. Methods: 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. Results: 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). Conclusions: 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. Keywords: Cancer stem cell, CD44, Programmed cell death ligand-1, Lung adenocarcinoma
*Correspondence: [email protected] † Chenyue Zhang and Hui Wang are first authors and contributed equally to this work 3 Department of Internal Medicine Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Number 440, Ji Yan Road, Jinan 250117, China Full list of author information is available at the end of the article
Background Lung cancer is the most lethal cancer worldwide with a 5-year survival rate of 15% [1]. Although adenocarcinoma (ADC) accounts for a large proportion of lung cancer, most ADC patients developed metastasis upon initial diagnosis, resulting in poor prognosis. Immunotherapy, aiming to enhance the host antitumor immune defense, has rendered prolonged survival in ADC [2].
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit
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