1. Academic Validation
  2. Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion

Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion

  • Oncoimmunology. 2022 Dec 22;12(1):2160558. doi: 10.1080/2162402X.2022.2160558.
Zi-Hao Wang 1 Pei Zhang 1 Wen-Bei Peng 1 Lin-Lin Ye 1 Xuan Xiang 1 Xiao-Shan Wei 1 Yi-Ran Niu 1 Si-Yu Zhang 1 Qian-Qian Xue 1 Hao-Lei Wang 1 Qiong Zhou 1
Affiliations

Affiliation

  • 1 Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Abstract

Malignant pleural effusion (MPE) is a functional 'cold' tumor microenvironment in which the antitumor activity of CD8+ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (Treg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA Sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3+ NKT-like cells. Similar to Treg cells, FOXP3+ NKT-like cells highly expressed Monocarboxylate Transporter 1 (MCT1) and Lactate Dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3+ NKT-like cells in human MPE.

Keywords

FOXP3; MCT1; Malignant pleural effusion; NKT-like cell; lactylation; scRNA-seq.

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