RÉSUMÉ
Oncolytic viruses (OVs) have shown potential in converting a "cold" tumor into a "hot" one and exhibit effectiveness in various cancer types. However, only a subset of patients respond to oncolytic virotherapy. It is important to understand the resistance mechanisms to OV treatment in pancreatic ductal adenocarcinoma (PDAC) to engineer oncolytic viruses. In this study, we used transcriptome RNA sequencing (RNA-seq) to identify Visfatin, which was highly expressed in the responsive tumors following OV treatment. To explore the antitumor efficacy, we modified OV-mVisfatin, which effectively inhibited tumor growth. For the first time, we revealed that Visfatin promoted the antitumor efficacy of OV by remodeling the tumor microenvironment, which involved enhancing CD8+ T cell and DC cell infiltration and activation, repolarizing macrophages towards the M1-like phenotype, and decreasing Treg cells using single-cell RNA sequencing (scRNA-seq) and flow cytometry. Furthermore, PD-1 blockade significantly enhanced OV-mVisfatin antitumor efficacy, offering a promising new therapeutic strategy for PDAC.
Sujet(s)
Herpèsvirus humain de type 1 , Nicotinamide phosphoribosyltransferase , Thérapie virale de cancers , Virus oncolytiques , Tumeurs du pancréas , Microenvironnement tumoral , Animaux , Tumeurs du pancréas/thérapie , Tumeurs du pancréas/anatomopathologie , Tumeurs du pancréas/génétique , Souris , Thérapie virale de cancers/méthodes , Nicotinamide phosphoribosyltransferase/génétique , Nicotinamide phosphoribosyltransferase/métabolisme , Herpèsvirus humain de type 1/génétique , Lignée cellulaire tumorale , Virus oncolytiques/génétique , Carcinome du canal pancréatique/thérapie , Carcinome du canal pancréatique/anatomopathologie , Carcinome du canal pancréatique/génétique , Carcinome du canal pancréatique/immunologie , Souris de lignée C57BL , Humains , Lymphocytes T CD8+/immunologie , Récepteur-1 de mort cellulaire programmée/antagonistes et inhibiteurs , Récepteur-1 de mort cellulaire programmée/génétique , Récepteur-1 de mort cellulaire programmée/métabolisme , FemelleSujet(s)
Anticorps neutralisants/immunologie , Vaccins contre la COVID-19/immunologie , COVID-19/immunologie , Glycoprotéine de spicule des coronavirus/immunologie , Anticorps antiviraux/immunologie , COVID-19/prévention et contrôle , COVID-19/virologie , Humains , SARS-CoV-2/immunologie , SARS-CoV-2/pathogénicité , Vaccins inactivés/immunologieRÉSUMÉ
Salmonella, a common foodborne pathogen, causes many cases of foodborne illness and poses a threat to public health worldwide. Immunological detection systems can be combined with nanoparticles to develop sensitive and portable detection technologies for timely screening of Salmonella infections. Here, we developed an antibody-probe-based immuno-N-hydroxysuccinimide (NHS) bead (AIB) system to detect Salmonella. After adding the antibody probe, Salmonella accumulated in the samples on the surfaces of the immuno-NHS beads (INBs), forming a sandwich structure (INB-Salmonella-probes). We demonstrated the utility of our AIB diagnostic system for detecting Salmonella in water, milk, and eggs, with a sensitivity of 9 CFU mL-1 in less than 50 min. The AIB diagnostic system exhibits highly specific detection and no cross-reaction with other similar microbial strains. With no specialized equipment or technical requirements, the AIB diagnostic method can be used for visual, rapid, and point-of-care detection of Salmonella.
