Transcriptomic profiling of immune cells in malignant pleural effusions identifies macrophage reprogramming associated with survival
7 affiliations
- 1Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
- 2Department of Biostatistics and Bioinformatics
- 3Department of Surgery
- 4Department of Integrative Immunobiology
- 5Department of Pathology
- 6Department of Medicine, Division of Medical Oncology; and
- 7Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
Abstract
Despite advances in treatment approaches for lung cancer, the morbidity and survival of patients with lung cancer with malignant pleural effusions (MPE) remain poor. This is in part due to gaps in understanding the role of immune cells in the pleural fluid microenvironment. We performed single-cell analysis with flow cytometry validation of CD45+ cells in 8 MPE and 5 benign pleural fluid effusion (BPE) specimens to identify changes in the transcriptomic landscape of immune cells across disease states. We found upregulation of proinflammatory signaling pathways, including IFN and TNF signaling, in T cells, B cells, and macrophages in benign compared with malignant pleural effusions. Proinflammatory HLA-DR+ macrophages were associated with good survival outcomes while protumorigenic HLA-DR– macrophages with upregulation of angiogenesis, TGF-β, and fibronectin signaling were associated with poor survival outcomes in patients with MPE. We also validated these findings with macrophage cell surface expression markers using flow cytometry in 14 MPE and 7 BPE specimens. Finally, we performed multiplex cytokine analysis, which showed enrichment of the type 3 inflammatory cytokine, IL-17A, in MPE as a putative mechanism for macrophage reprogramming. These data provide a rich resource for interrogating the immune cell types and states present across the spectrum of pleural disease. They offer not only prognostic value for patient outcomes at the time of pleural fluid collection but also insights into novel immunotherapy targets.
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BibTeX
@article{khatri2026transcriptomic,
title = {{Transcriptomic profiling of immune cells in malignant pleural effusions identifies macrophage reprogramming associated with survival}},
author = {Aaditya Khatri and Huimin Wang and Zhicheng Ji and Prekshaben Patel and Smita K. Nair and Javid P. Mohammed and Beth H. Shaz and Andrew B. Nixon and Scott M. Palmer and Kamran Mahmood},
journal = {JCI Insight},
year = {2026},
month = sep,
doi = {10.1172/jci.insight.201691},
url = {https://doi.org/10.1172/jci.insight.201691},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptomic profiling of immune cells in malignant pleural effusions identifies macrophage reprogramming associated with survival
AU - Aaditya Khatri
AU - Huimin Wang
AU - Zhicheng Ji
AU - Prekshaben Patel
AU - Smita K. Nair
AU - Javid P. Mohammed
AU - Beth H. Shaz
AU - Andrew B. Nixon
AU - Scott M. Palmer
AU - Kamran Mahmood
PY - 2026
DA - 2026/09/15
JO - JCI Insight
DO - 10.1172/jci.insight.201691
UR - https://doi.org/10.1172/jci.insight.201691
AB - Despite advances in treatment approaches for lung cancer, the morbidity and survival of patients with lung cancer with malignant pleural effusions (MPE) remain poor. This is in part due to gaps in understanding the role of immune cells in the pleural fluid microenvironment. We performed single-cell analysis with flow cytometry validation of CD45+ cells in 8 MPE and 5 benign pleural fluid effusion (BPE) specimens to identify changes in the transcriptomic landscape of immune cells across disease states. We found upregulation of proinflammatory signaling pathways, including IFN and TNF signaling, in T cells, B cells, and macrophages in benign compared with malignant pleural effusions. Proinflammatory HLA-DR+ macrophages were associated with good survival outcomes while protumorigenic HLA-DR– macrophages with upregulation of angiogenesis, TGF-β, and fibronectin signaling were associated with poor survival outcomes in patients with MPE. We also validated these findings with macrophage cell surface expression markers using flow cytometry in 14 MPE and 7 BPE specimens. Finally, we performed multiplex cytokine analysis, which showed enrichment of the type 3 inflammatory cytokine, IL-17A, in MPE as a putative mechanism for macrophage reprogramming. These data provide a rich resource for interrogating the immune cell types and states present across the spectrum of pleural disease. They offer not only prognostic value for patient outcomes at the time of pleural fluid collection but also insights into novel immunotherapy targets.
SN - 2379-3708
ER -