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Characterizing soluble immune checkpoint molecules and TGF-β1,2,3 in pleural effusion of malignant pleural

Riki Okita1, Tomoya Senoo2, Yuka Mimura-Kimura3

  • 1Department of Thoracic Surgery, National Hospital Organization Yamaguchi Ube Medical Center, Higashikiwa 685, Ube, Yamaguchi, 755-0241, Japan. riki0716okita@yahoo.co.jp.

Scientific Reports
|July 10, 2024
PubMed

Insights

Soluble TGF-β2 in pleural fluid can differentiate malignant pleural mesothelioma from fibrinous pleuritis. TGF-β1 and TGF-β3 show prognostic value for mesothelioma, while soluble PD-1 levels predict anti-PD1 therapy response.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • The clinical significance of soluble molecules in pleural effusion (PE) for malignant pleural mesothelioma (MPM) remains largely undefined.
  • Understanding these biomarkers is crucial for improving diagnosis, prognosis, and treatment strategies in MPM.

Purpose of the Study:

  • To investigate the role of soluble cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), PD-1 ligand 1 (PD-L1), and TGF-β isoforms in pleural effusion of MPM and fibrinous pleuritis (FP) patients.
  • To assess the relationships between these soluble molecules, clinicopathological characteristics, and the efficacy of immune checkpoint inhibitors (ICIs).

Main Methods:

  • A retrospective observational study involving 79 MPM and 34 FP patients.
  • Enzyme-linked immunosorbent assays (ELISAs) were used to measure soluble CTLA-4, PD-1, and PD-L1.
  • Multiplex assays quantified three TGF-β isoforms (TGF-β1, TGF-β2, TGF-β3) in pleural effusion samples.

Main Results:

  • Soluble CTLA-4, PD-L1, PD-1, TGF-β1, TGF-β2, and TGF-β3 were detected in PE of both FP and MPM patients, with significant correlations to clinicopathological features.
  • Soluble immune checkpoint molecules did not demonstrate diagnostic or prognostic utility in MPM.
  • Soluble TGF-β2 in PE served as a differential diagnostic marker between FP and MPM.
  • Soluble TGF-β1 and TGF-β3 levels emerged as promising prognostic markers for MPM.
  • Elevated baseline soluble PD-1 levels predicted a positive response to anti-PD1 monotherapy.

Conclusions:

  • Soluble TGF-β2 is a valuable differential diagnostic biomarker for distinguishing malignant pleural mesothelioma from fibrinous pleuritis.
  • Soluble TGF-β1 and TGF-β3 are potential prognostic biomarkers for malignant pleural mesothelioma.
  • Baseline soluble PD-1 levels may predict treatment response in patients undergoing anti-PD1 monotherapy for MPM, identifying novel biomarkers for diagnosis, prognosis, and predictive therapy selection.
Keywords:
Immune checkpoint moleculeMesotheliomaPleural effusionTGF-βTumor immune microenvironment

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