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Frontiers | Enterovirus 71 Antagonizes Antiviral Effects of Type III Interferon and Evades the Clearance of Intestinal Intraepithelial Lymphocytes

Enterovirus 71 (EV71) is the major pathogen causing severe neurological complications, hand, foot, and mouth disease. The intestinal mucosal immune system has a complete immune response and immune regulation mechanism, consisting of densely arranged monolayer intestinal epithelial cells (IECs) and intestinal intraepithelial lymphocytes (iIELs) distributed among the IECs, which constitute the first line of intestinal mucosa against infection of foreign pathogens. As an enterovirus, EV71 is transmitted by the intestinal tract; however, the mechanisms it uses to evade the immunosurveillance of the intestinal mucosal immune system are still incompletely clarified. The present study investigated how EV71 evades from recognizing and eliminating IECs, iIELs, and iNK cells. We found that EV71 infection-induced higher level of type III interferons (IFN-λ) than type Ⅰ interferons (IFN-β) in IECs and the addition of IFN-λ markedly restricted EV71 replication in IECs. These results indicate t ....

South Korea , United States , United Kingdom , Uppsala Lan , Jianwei Wang , Hanzhong Wang , Bingqing Li , Van Kaer , Peprotech Cranbury , Pamps Peterson , National Natural Science Foundation Of China , Shandong Provincial Natural Science Foundation , Institute Of Basic Medicine , Institute Of Pathogen Microbiology , Chinese Academy Of Sciences , Treestar Inc , National Major Science Technology Project For , Chinese Academy Of Medical Sciences , Wuhan Institute Of Virology , Ge Healthcare , Beckman Coulter Inc , Wuhan Institute , Chinese Academy , Minimum Essential Modified , Beijing Four Rings Bio Pharmaceutical , Pathogen Microbiology ,

B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumor-infiltrating lymphocytes


Abstract
Cancer immunotherapy with 4-1BB agonists has limited further clinical development because of dose-limiting toxicity. Here, we developed a bispecific antibody (bsAb; B7-H3×4-1BB), targeting human B7-H3 (hB7-H3) and mouse or human 4-1BB, to restrict the 4-1BB stimulation in tumors. B7-H3×m4-1BB elicited a 4-1BB–dependent antitumor response in hB7-H3–overexpressing tumor models without systemic toxicity. BsAb primarily targets CD8 T cells in the tumor and increases their proliferation and cytokine production. Among the CD8 T cell population in the tumor, 4-1BB is solely expressed on PD-1 ....

United States , South Korea , Republic Of Korea , Tonbo Biosciences , Eomes Dan , Spectrostar Nano , Cytofix Cytoperm , Lab Inc , Ge Healthcare Life Sciences , Biocytogen Haimen Animal Center , Korean Cell Line Bank , Cell Signaling Technology , Treestar Inc , Precisionx Ray Inc , Donga St Co , Ge Healthcare , Ministry Of Education , Graphpad Prism Software , Biotech Center , Jiangsu Biocytogen Co , Tp Bio Co , Orient Bio Inc , Bio Inc , University Of Ulsan , Biacore Insight Evaluation Software Cytiva , Biocytogen Co ,