Complex Evaluation of Surfactant Protein A and D as Biomarkers for the Severity of COPD.

Purpose: Pulmonary surfactant proteins A (SP-A) and D (SP-D) are lectins, involved in host defense and regulation of pulmonary inflammatory response. However, studies on the assessment of COPD progress are limited. Patients and Methods: Pulmonary surfactant proteins were obtained from the COPD mouse model induced by cigarette and lipopolysaccharide, and the specimens of peripheral blood and bronchoalveolar lavage (BALF) in COPD populations. H&E staining and RT-PCR were performed to demonstrate the successfully established of the mouse model. The expression of SP-A and SP-D in mice was detected by Western Blot and immunohistochemistry, while the proteins in human samples were measured by ELISA. Pulmonary function test, inflammatory factors (CRP, WBC, NLR, PCT, EOS, PLT), dyspnea index score (mMRC and CAT), length of hospital stay, incidence of complications and ventilator use were collected to assess airway remodeling and progression of COPD. Results: COPD model mice with emphysema and airway wall thickening were more prone to have decreased SP-A, SP-D and increased TNF-α, TGF-ß, and NF-kb in lung tissue. In humans, SP-A and SP-D decreased in BALF, but increased in serum. The serum SP-A and SP-D were negatively correlated with FVC, FEV1, FEV1/FVC, and positively correlated with CRP, WBC, NLR, mMRC and CAT scores (P < 0.05, respectively). The lower the SP-A and SP-D in BALF, the worse the lung function and the increased probability of complications and ventilator use. Moreover, the same trend emerged in COPD patients grouped according to GOLD severity grade (Gold 1-2 group vs Gold 3-4 group). The worse the patient's condition, the more pronounced the change. Conclusion: This study suggests that SP-A and SP-D may be related to the progression and prognostic evaluation of COPD in terms of airway remodeling, inflammatory response and clinical symptoms, and emphasizes the necessity of future studies of surfactant protein markers in COPD.

In situ self-assembled peptide enables effective cancer immunotherapy by blockage of CD47.

Treatment of late-stage lung cancer has witnessed limited advances. In contrast to the tremendous efforts toward improving adaptive immunity, approaches to modulating innate immunity are relatively immature. As important innate immune cells, tumor-associated macrophages (TAMs) account for a substantial fraction of tumor-infiltrating lymphocytes, which not only reverses the immune-suppressive tumor microenvironment but also facilitates an adaptive immune response. In this study, we developed a tumor-specific MMP-2-responsive CD47 blockage (TMCB) strategy to enable effective cancer immunotherapy. Briefly, the matrix metalloproteinase-2 (MMP-2)-responsive self-assembly peptide specifically recognizes CD47, which is highly expressed in lung tumor cells. Second, the MMP-2-responsive self-assembly peptide is efficiently cleaved by MMP-2, which is overexpressed in the tumor microenvironment. Finally, the generated residual peptide naturally self-assembles into peptide-based nanofibers. The in situ constructed nanofibers inhibit the canonical CD47 "Do not eat me" signal expressed on tumor cells to promote phagocytosis of tumor cells by macrophages, which further induces effective antigen presentation and initiates T cell-mediated adaptive immune responses to inhibit tumor growth. Thus, we described a peptide-based TMCB strategy that induces both innate and adaptive immune systems to inhibit tumor growth.