id:"swepub:oai:DiVA.org:uu-376719"
Sökning: id:"swepub:oai:DiVA.org:uu-376719" > IL-6 Signaling Bloc...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03972naa a2200361 4500 | |
| 001 | oai:DiVA.org:uu-376719 | |
| 003 | SwePub | |
| 008 | 190211s2019 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3767192 URI |
| 024 | 7 | a https://doi.org/10.4049/jimmunol.18007172 DOI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Eriksson, Emmau Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)emmsv898 |
| 245 | 1 0 | a IL-6 Signaling Blockade during CD40-Mediated Immune Activation Favors Antitumor Factors by Reducing TGF-beta, Collagen Type I, and PD-L1/PD-1 |
| 264 | c 2019-02-01 | |
| 264 | 1 | b AMER ASSOC IMMUNOLOGISTS,c 2019 |
| 338 | a print2 rdacarrier | |
| 520 | a IL-6 plays a role in cancer pathogenesis via its connection to proteins involved in the formation of desmoplastic stroma and to immunosuppression by driving differentiation of myeloid suppressor cells together with TGF-beta. Inhibition of IL-6 signaling in the tumor microenvironment may, thus, limit desmoplasia and myeloid suppressor cell differentiation. CD40 signaling can further revert myeloid cell differentiation toward antitumor active phenotypes. Hence, the simultaneous use of IL-6 blockade with CD40 stimuli may tilt the tumor microenvironment to promote antitumor immune responses. In this paper, we evaluated the mechanisms of LOAd713, an oncolytic adenovirus designed to block IL-6R signaling and to provide myeloid cell activation via a trimerized membrane-bound isoleucine zipper (TMZ) CD40L. LOAd713-infected pancreatic cancer cells were killed by oncolysis, whereas infection of stellate cells reduced factors involved in stroma formation, including TGF-beta-1 and collagen type I. Virus infection prevented IL-6/GM-CSF-mediated differentiation of myeloid suppressors, but not CD163 macrophages, whereas infection of dendritic cells led to upregulation of maturation markers, including CD83, CD86, IL-12p70, and IFN-gamma. Further, IL-6R blockade prevented upregulation of programed death ligand 1 (PD-L1) and PD-1 on the stimulated dendritic cells. These results suggest that LOAd713 can kill infected tumor cells and has the capacity to affect the tumor microenvironment by stimulating stellate cells and myeloid suppressors with TMZ-CD40L and IL-6R blockade. Gene transfer of murine TMZ-CD40L prolonged survival in an animal model. LOAd713 may be an interesting therapeutic option for cancers connected to IL-6 signaling, such as pancreatic cancer. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng |
| 700 | 1 | a Milenova, Ioannau Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)yoami964 |
| 700 | 1 | a Wenthe, Jessicau Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)jeswe849 |
| 700 | 1 | a Moreno, Rafaelu Inst Catala Oncol, Inst Invest Biomed Bellvitge, Barcelona 08908, Spain4 aut |
| 700 | 1 | a Alemany, Ramonu Inst Catala Oncol, Inst Invest Biomed Bellvitge, Barcelona 08908, Spain4 aut |
| 700 | 1 | a Loskog, Angelica S.,d 1973-u Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Lokon Pharma AB, S-75183 Uppsala, Sweden4 aut0 (Swepub:uu)angelosk |
| 710 | 2 | a Uppsala universitetb Klinisk immunologi4 org |
| 773 | 0 | t Journal of Immunologyd : AMER ASSOC IMMUNOLOGISTSg 202:3, s. 787-798q 202:3<787-798x 0022-1767x 1550-6606 |
| 856 | 4 | u https://www.jimmunol.org/content/jimmunol/202/3/787.full.pdf |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-376719 |
| 856 | 4 8 | u https://doi.org/10.4049/jimmunol.1800717 |
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