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Background. The activation of complement is involved in monocyte recruitment in tuberculous pleural effusion (TPE), while the role of the cleavage product of complement C3 in this process needs further research. Methods. The expression of complement components in pleural biopsy specimens of TPE patients was measured. The concentration of cleavage products of complement was tested in TPE by ELISA. Moreover, the colocalizations of C3b and CR1, C3d and CR3, and CXCL12 and CXCR4 in monocytes and pleural mesothelial cells (PMCs) isolated from TPE were determined by an immunofluorescent assay. Monocyte chemotaxis assay was analyzed via transwell chambers. Results. Three pathways of the complement system were activated in tuberculous pleurisy. In patients with TPE, C3 lysis was more active than peripheral blood in pleural cavity. Tuberculous protein Mpt64 and anaphylatoxin C3a could significantly promote CXCL12 production in human PMCs isolated from TPE. C3b-CR1, C3d-CR3, and CXCL12-CXCR4 were colocalized in PMCs and monocytes from TPE. The recruitment of monocytes into TPE mediated by PMCs could be inhibited by anti-CR1, anti-CR3, and anti-CXCL12 monoclonal antibodies (mAbs). Conclusions. Complement activates strongly in TPE, and PMCs induced monocytes to the pleural cavity through C3a, C3b, and C3d. [ABSTRACT FROM AUTHOR]

Objectives: Despite remarkable advances in the treatment of non‐small cell lung cancer (NSCLC) with anti‐programmed death (PD)‐1 therapy; only a fraction of patients derives durable clinical benefit. In this study, we investigated whether the differentiation status of systemic CD8+ T cells predicts the outcome of PD‐1 blockade in NSCLC. Methods: We carried out a prospective study on a total of 77 NSCLC patients receiving anti‐PD‐1 blockers, among which 47 patients were assigned as a discovery cohort and 30 patients as a validation cohort. Peripheral blood samples were obtained at baseline and upon multiple therapy cycles and analyzed by multi‐parameter flow cytometry. Results: We found that a higher baseline ratio of PD‐1+ early effector memory CD8+ T cells (CD28+CD27−CD45RO+, TEEM) to PD‐1+ effector CD8+ T cells (CD28−CD27−CD45RO−, TE) delineated responders to PD‐1 blockade from progressors and was associated with prolonged progression‐free survival (PFS) and durable clinical benefit. Moreover, PD‐1+CD8 TEEM cells exhibited early responses after anti‐PD‐1 therapy and was the major fraction of cycling PD‐1+Ki67+CD8+ T cells to expand specifically with positive impact on PFS. Conclusion: These findings provide insights into how the baseline differentiation status of the peripheral immune system determines responses to PD‐1‐targeted therapies. [ABSTRACT FROM AUTHOR]

Objectives: Despite remarkable advances in the treatment of non-small cell lung cancer (NSCLC) with anti-programmed death (PD)-1 therapy; only a fraction of patients derives durable clinical benefit. In this study, we investigated whether the differentiation status of systemic CD8 + T cells predicts the outcome of PD-1 blockade in NSCLC., Methods: We carried out a prospective study on a total of 77 NSCLC patients receiving anti-PD-1 blockers, among which 47 patients were assigned as a discovery cohort and 30 patients as a validation cohort. Peripheral blood samples were obtained at baseline and upon multiple therapy cycles and analyzed by multi-parameter flow cytometry., Results: We found that a higher baseline ratio of PD-1 + early effector memory CD8 + T cells (CD28 + CD27 - CD45RO + , T EEM ) to PD-1 + effector CD8 + T cells (CD28 - CD27 - CD45RO - , T E ) delineated responders to PD-1 blockade from progressors and was associated with prolonged progression-free survival (PFS) and durable clinical benefit. Moreover, PD-1 + CD8 T EEM cells exhibited early responses after anti-PD-1 therapy and was the major fraction of cycling PD-1 + Ki67 + CD8 + T cells to expand specifically with positive impact on PFS., Conclusion: These findings provide insights into how the baseline differentiation status of the peripheral immune system determines responses to PD-1-targeted therapies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

SERPINE2, also known as protease nexin-1 (PN-1), is a serine protease inhibitor produced by many cell types and has pleiotropic biological functions. It has been reported that SERPINE2/PN-1 is involved in tissue remodeling of fibrotic diseases including idiopathic pulmonary fibrosis and cardiac fibrosis. However, the potential role of SERPINE2/PN-1 in asthmatic airway remodeling has remained barely investigated so far. In this study, BALB/c male mice were sensitized and challenged by ovalbumin to generate murine models of airway remodeling. Anti-SERPINE2 monoclonal antibody was intraperitoneally injected into these mice during the ovalbumin challenge while IgG antibody was used as a vehicle control. The results revealed that the expression of SERPINE2/PN-1 was significantly upregulated in the lung extracts of ovalbumin-challenged mice, and this upregulation was inhibited by dexamethasone. Sustained ovalbumin stimulation increased the thickness of airway wall and α-SMA positive areas in lung, which was attenuated by the treatment with SERPINE2 antibody. In addition, SERPINE2 antibody partially blocked the phosphorylation of ERK, and reduced the upregulation of MMP-9 and TIMP-1 expressions in asthmatic mice. These findings suggest that SERPINE2/PN-1 may play a role in the pathologic development of airway remodeling. Monoclonal antibody against SERPINE2 may have the potential as an effective pharmacotherapy for asthmatic airway remodeling., Competing Interests: None., (IJCEP Copyright © 2017.)