Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. www.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf?ua=1 WHO global tuberculosis report. 2015
    1. Porcel JM. Tuberculous pleural effusion. Lung. 2009;187:263–270. doi: 10.1007/s00408-009-9165-3. - DOI - PubMed
    1. Valdés L, Pose A, San José E, Vázquez JM Martínez. Tuberculous pleural effusions. Eur J Intern Med. 2003;14:77–88. doi: 10.1016/S0953-6205(03)00018-9. - DOI - PubMed
    1. Khan FY, Hamza M, Omran AH, Saleh M, Lingawi M, Alnaqdy A, Rahman MO, Ahmedullah HS, Hamza A, Ani AA, et al. Diagnostic value of pleural fluid interferon-gamma and adenosine deaminase in patients with pleural tuberculosis in Qatar. Int J Gen Med. 2013;6:13–18. doi: 10.2147/IJGM.S39345. - DOI - PMC - PubMed
    1. Azimi Q, Rezadoost B, Nadoushan M Jalali, Davati A. Evaluation of serum cyfra21-1 in patients with pleural effusion. Iran Red Crescent Med J. 2012;14:613–616. - PMC - PubMed

LinkOut - more resources