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CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion

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A Correction to this article was published on 04 August 2021

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Abstract

Background

Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis.

Methods

Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, respectively. Flow cytometry was performed to analyze cell phenotypes, and RT-qPCR was used to detect cytokine expression in these monocytes and macrophages. A blinded validation study (n = 40) was subsequently performed to confirm the significance of CD163+CD14+ TAMs in MPE diagnosis. Student’s t test, rank sum test, and receiver operating characteristic curve analysis were used for statistical analysis.

Results

Notably, CD163+CD14+ cell frequency in MPE was remarkably higher than that in NMPE (P < 0.001). In a blinded validation study, a sensitivity of 78.9 % and a specificity of 100 % were obtained with CD163+CD14+ TAMs as a MPE biomarker. In total (n = 140), by using a cutoff level of 3.65 %, CD163+CD14+ cells had a sensitivity of 81.2 % and a specificity of 100 % for MPE diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural effusion could be obtained one week earlier than that obtained by cytological examination.

Conclusions

CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis.

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Abbreviations

AUC:

Area under curve

CI:

Confidence interval

FACS:

Fluorescence-activating cell sorter

MACS:

Magnetic cell sorting

MDSC:

Myeloid-derived suppressor cells

MPE:

Malignant pleural effusion

NMPE:

Non-malignant pleural effusion

NS:

Normal saline

RCC:

Renal cell carcinoma

ROC:

Receiver operating characteristic curve

SPSS:

Statistical program for social sciences

TAMs:

Tumor-associated macrophages

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81171986, 81271815, 812111102), Research grant from the Ministry of Public Health (Grant No. 20110110001), the Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province (Grant Nos. 112300410153, 122300410155), Funds for Creative Research Team of Henan Province, Creative Research Team of Higher Education of Henan Province, and the Innovation Team of The First Affiliated Hospital of Zhengzhou University.

Conflict of interest

All authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China

      Fei Wang, Li Yang, Qun Gao, Lan Huang & Yi Zhang

    2. School of Life Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou, 450001, Henan Province, China

      Fei Wang & Yi Zhang

    3. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China

      Qun Gao, Liping Wang & Yi Zhang

    4. Department of Respiration, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, China

      Jing Wang

    5. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

      Shengdian Wang

    6. Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

      Bin Zhang

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    1. Fei Wang
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    Fei Wang and Li Yang have contributed equally to this work.

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    Wang, F., Yang, L., Gao, Q. et al. CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion. Cancer Immunol Immunother 64, 965–976 (2015). https://doi.org/10.1007/s00262-015-1701-9

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