Characterizing soluble immune checkpoint molecules and TGF-β 1,2,3 in pleural effusion of malignant pleural mesothelioma

Abstract The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-β isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the six molecules, clinicopathological characteristics, and its efficacy as an immune checkpoint inhibitor. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-β1 TGF-β2 and TGF-β3 were variably produced in PE of FP (n=34) and MPM (n=79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-β2 levels in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-1 and TGF-3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.