Diagnostic value of CD206+CD14+ macrophages in diagnosis of lung cancer originated malignant pleural effusion

Pei, Xue-Bin; Wu, Xiu‐Zhi; Yi, Facheng; Zhai, Kan; Shi, Honglei

doi:10.21037/jtd.2019.06.44

Cited by 11 publications

(6 citation statements)

References 26 publications

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“…Macrophages are one type of main immune cells infiltrating into MPE and present a wide range of M1/M2 spectrum ( 31 ). Consistent with previous studies ( 32 – 34 ), our present study confirmed that macrophages in MPE were characterized by M2-polarized phenotype. Although the immunoregulatory function of macrophages have been illustrated in most tumor models, the underlying role of macrophages in MPE remains to be clarified.…”

Section: Discussionsupporting

confidence: 93%

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion

et al. 2023

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IntroductionTumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined.MethodsMPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival.ResultsSingle-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process.ConclusionsTaken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.

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Section: Discussionsupporting

confidence: 93%

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion

et al. 2023

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“…1C). When Mφs, which are known to accumulate in MPE ( 16 ), ingest apoptotic cells, they are educated to acquire an anti- inflammatory phenotype, often associated with a protumorigenic function ( 17 ). However, whether clearance of apoptotic cells by Mφs, rather than a direct mechanism of cancer cell immune evasion, controls MPE progression has not yet been tested.…”

Section: Resultsmentioning

confidence: 99%

Efferocytosis fuels malignant pleural effusion through TIMP1

et al. 2021

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Malignant pleural effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. No effective treatments are currently available, reflecting our insufficient understanding of the basic mechanisms leading to MPE progression. Here, we found that efferocytosis through the receptor tyrosine kinases AXL and MERTK led to the production of interleukin-10 (IL-10) by four distinct pleural cavity macrophage (Mφ) subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of Axl and Mertk in Mφs or IL-10 receptor in DCs or Timp1 substantially reduced MPE progression. Our results delineate an inflammatory cascade—from the clearance of apoptotic cells by Mφs, to production of IL-10, to induction of TIMP1 in DCs—that facilitates MPE progression. This inflammatory cascade offers a series of therapeutic targets for MPE.

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“…At a threshold of 3.65%, the diagnostic sensitivity and specificity of CD14 + D163 + macrophages were 0.86 and 1.00, respectively (82). In another study, the authors investigated the diagnostic accuracy of CD206 + CD14 + macrophages for lung cancer-induced MPE (83), reporting an AUC as high as 0.98, with 0.88 sensitivity and 1.00 specificity at a 39.8% threshold.…”

Section: Tumor-associated Macrophages (Tams) and Monocytesmentioning

confidence: 99%

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

Zhang¹,

Li²,

Lippi³

et al. 2021

Transl Lung Cancer Res

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Although cytology and pleural biopsy of pleural effusion (PE) are the gold standards for diagnosing malignant pleural effusion (MPE), these tools' diagnostic accuracy is plagued by some limitations such as low sensitivity, considerable inter-observer variation and invasiveness. The assessment of PE biomarkers may hence be seen as an objective and non-invasive diagnostic alternative in MPE diagnostics. In this review, we summarize the characteristics and diagnostic accuracy of available PE biomarkers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigens 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), a fragment of cytokeratin 19 (CYFRA 21-1), chitinase-like proteins (CLPs), vascular endothelial growth factor (VEGF) and its soluble receptor, endostatin, calprotectin, cancer ratio, homocysteine, apolipoprotein E (Apo-E), B7 family members, matrix metalloproteinase (MMPs) and tissue-specific inhibitors of metalloproteinases (TIMPs), reactive oxygen species modulator 1 (Romo1), tumor-associated macrophages (TAMs) and monocytes, epigenetic markers (e.g., cell-free microRNA and mRNA). We summarized the evidence from systematic review and meta-analysis for traditional tumor markers' diagnostic accuracy. According to the currently available evidence, we conclude that the traditional tumor markers have high specificity (around 0.90) but low sensitivity (around 0.50). The diagnostic accuracy of novel tumor markers needs to be validated by further studies. None of these tumor biomarkers would have sufficient diagnostic accuracy to confirm or exclude MPE when used alone. A multi-biomarker strategy, also encompassing the use of artificial intelligence algorithms, may be a valuable perspective for improving the diagnostic accuracy of MPE.

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Diagnostic value of CD206+CD14+ macrophages in diagnosis of lung cancer originated malignant pleural effusion

Cited by 11 publications

References 26 publications

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion

Efferocytosis fuels malignant pleural effusion through TIMP1

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

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