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. 2016 Oct;12(4):2161-2168.
doi: 10.3892/etm.2016.3611. Epub 2016 Aug 23.

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

Xue Pan  1 , Anyuan Zhong  1 , Yufei Xing  1 , Minhua Shi  1 , Bin Qian  1 , Tong Zhou  1 , Yongjing Chen  2 , Xueguang Zhang  2
Affiliations

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

Xue Pan et al. Exp Ther Med. 2016 Oct.

Abstract

Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T lymphocytes and cluster of differentiation (CD)14+ monocytes were co-cultured to investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD-L1 and PD-L1 on CD14+ monocytes were increased in the TPE group, as compared with the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels of PD-L1 on CD14+ monocytes were demonstrated to be positively correlated with interferon (IFN)-γ concentration in pleural effusions. Therefore, IFN-γ may increase the expression of PD-L1 on CD14+ monocytes in vitro. Cell counting kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially reverse the proliferation of T lymphocytes in the co-culture system. The results of the present study indicated that sPD-L1 or mPD-L1 are associated with the immune regulation and disease progression of TPE, and may serve as possible biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway suggests a potential immune therapy strategy for the treatment of TPE.

Keywords: antibody; interferon-γ; programmed death ligand-1; soluble programmed death ligand-1; tuberculous pleural effusion.

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Figures

Figure 1.
Figure 1.
Expression of PD-L1 on CD14+ monocytes, as detected by flow cytometry. (A) Total distribution of pleural effusion monocyte cells from the subject who was diagnosed with tuberculous pleural effusion. (B) Expression of CD14+ monocytes in the proportion of region marked in (A). (C) Expression of PD-L1 on CD14+ monocytes in the region marked in (B). TPE, MPE and n-TB n-M demonstrate the expression of PD-L1 on CD14+ monocytes in different pleural effusions by flow cytometry. PD-L1, programmed death ligand-1; CD, cluster of differentiation; TPE, tuberculous pleural effusion; MPE, malignant pleural effusion; n-TB n-M, non-TB non-M pleural effusion.
Figure 2.
Figure 2.
(A) Expression of sPD-L1 in PB and PF. (B) Expression of sPD-L1 in PF and PB in patients diagnosed with TPE. (C) Expression of sPD-L1 in the TPE, MPE and n-TB n-M groups. (D) Expression of sPD-L1 in patients diagnosed with TPE and non-TPE. (E) Expression of IFN-γ in the TPE, MPE and n-TB n-M groups. (F) Expression of IFN-γ in patients diagnosed with TPE and non-TPE. **P<0.05; ***P<0.0001. sPD-L1, sPD-L1, soluble programmed death ligand-1; PF, pleural effusion; PB, peripheral blood; TPE, tuberculous pleural effusion; MPE, malignant pleural effusion; n-TB n-M, non-TB non-M pleural effusion; IFN, interferon.
Figure 3.
Figure 3.
(A) PBMCs were supplemented with TPE and co-cultured for 48 h, and the expression levels of PD-L1 on CD14+ monocytes were subsequently analyzed by flow cytometry. (B) A significant correlation was detected between IFN-γ and PD-L1 on CD14+ monocytes in pleural effusion (P<0.0001) and (C) sPD-L1 and IFN-γ in pleural effusion (P=0.0004), respectively. (D) Effect of anti-PD-L1 monoclonal antibodies on the proliferation of T cells following 96-h co-cultivation with CD14+ monocytes was evaluated with a cell counting kit-8. *P<0.0001, as compared with the T group; **P=0.005, as compared with the T+CD3+M group. PBMCs, peripheral blood monocyte cells; TPE, tuberculous pleural effusion; PD-L1, programmed death ligand −1; CD, cluster of differentiation; sPD-L1, soluble PD-L1; IFN, interferon; T, T cells; CD3, agonistic CD3 antibody; M, monocytes that were separated from TPE; mIgG, mouse anti-human immunoglobulin G control antibody; 2H11, mouse anti-human PD-L1 antibody.
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