RESUMEN
T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.
RESUMEN
OBJECTIVE To evaluate the effect of antiviral agents in treating of severe acute respiratory syndrome(SARS). METHODS Based on the particular data (including medical history,examiuations and treatments) of 1702 patients of with SARS which were offered by the Health Bureau of Guangdong Province,the inpact factors of death and the course of diseases of SARS were retrospectively analyzed with unifactorial and multifactors statistic analysis methods. RESULTS It did not show any signs that the death rate could be decreased by the six antiviral agents in common use,but vidarabine could help to shorten the course of disease(OR=1.399,P=0.025),while oseltamivir might be prolonged the course of disease(OR=0.708,P=0.000). CONCLUSIONS The data showed that the effect of the six antiviral agents for curing SARS is limited,and a new antiviral treatment for SARS should be explored further.