bStaphylococcus aureus is a common pathogen found in the community and in hospitals. Most notably, methicillin-resistant S. aureus is resistant to many antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments, such as immunotherapeutic approaches. To date, most clinical trials of vaccines or of passive immunization against S. aureus have ended in failure. In this study, we investigated two ESAT-6-like proteins secreted by S. aureus, S. aureus EsxA (SaEsxA) and SaEsxB, as possible targets for a vaccine. Mice vaccinated with these purified proteins elicited high titers of anti-SaEsxA and anti-SaEsxB antibodies, but these antibodies could not prevent S. aureus infection. On the other hand, recombinant SaEsxA (rSaEsxA) and rSaEsxB could induce Th1-and Th17-biased immune responses in mice. Mice immunized with rSaEsxA and rSaEsxB had significantly improved survival rates when challenged with S. aureus compared with the controls. These findings indicate that SaEsxA and SaEsxB are two promising Th1 and Th17 candidate antigens which could be developed into multivalent and serotype-independent vaccines against S. aureus infection.
Programmed death ligand-1 (PD-L1) is expressed on the surface of tumor cells and binds to programmed cell death protein-1 (PD1) on the surface of T cells, leading to cancer immune evasion via inhibition of T cell function. One of the characteristics of small cell lung cancer (SCLC) is its ineffective anti-tumor immune response and highly immunosuppressive status in the tumor microenvironment. SCLC cells have been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that SCLC EVs may be important mediators of immunosuppression and that PD-L1 could play a role. Herein, we showed that PD-L1 was expressed on the surface of SCLC-derived EVs, with the potential to directly bind to PD1. Experimentally, we further showed that EVs secreted by SCLC cells can inhibit CD8 + T cell activation and cytokine production in vitro in response to T cell receptor stimulation. Importantly, an anti-PD-L1 blocking antibody significantly reversed the EVs-mediated inhibition of CD8 + T cell activation. Furthermore, we performed a retrospective study of patients with SCLC to determine the prognostic value of PD-L1 harvested from plasm circulating EVs. The results showed that EVs containing PD-L1 was an independent prognostic factor and significantly correlated with progression-free survival (PFS). Together, these results indicate that EVs containing PD-L1 can be served as a diagnostic biomarker for predicting the effectiveness of therapy, as well as a new strategy to enhance T cell-mediated immunotherapy against SCLC cancers.
Previous studies show that, in quantum chaotic and integrable systems, the so-called out-of-timeordered correlator (OTOC) generically behaves differently at long times, while, it may show similar early growth in one-body systems. In this paper, by means of numerical simulations, it is shown that OTOC has similar early growth in two quantum many-body systems, one integrable and one chaotic.
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