Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy
Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
01 May 2020
|
| In: |
Nature Communications
Year: 2020, Jahrgang: 11 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-15979-2 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1038/s41467-020-15979-2 Verlag: https://www.nature.com/articles/s41467-020-15979-2 
|
| Verfasserangaben: | Daniel Baumann, Tanja Hägele, Julian Mochayedi, Jennifer Drebant, Caroline Vent, Sven Blobner, Julia Han Noll, Irena Nickel, Corinna Schumacher, Sophie Luise Boos, Aline Sophie Daniel, Susann Wendler, Michael Volkmar, Oliver Strobel, Rienk Offringa |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1713927888 | ||
| 003 | DE-627 | ||
| 005 | 20240406193238.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200708s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-020-15979-2 |2 doi | |
| 035 | |a (DE-627)1713927888 | ||
| 035 | |a (DE-599)KXP1713927888 | ||
| 035 | |a (OCoLC)1341344973 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Baumann, Daniel |e VerfasserIn |0 (DE-588)1186002131 |0 (DE-627)1665288558 |4 aut | |
| 245 | 1 | 0 | |a Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy |c Daniel Baumann, Tanja Hägele, Julian Mochayedi, Jennifer Drebant, Caroline Vent, Sven Blobner, Julia Han Noll, Irena Nickel, Corinna Schumacher, Sophie Luise Boos, Aline Sophie Daniel, Susann Wendler, Michael Volkmar, Oliver Strobel, Rienk Offringa |
| 264 | 1 | |c 01 May 2020 | |
| 300 | |a 18 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 08.07.2020 | ||
| 520 | |a Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T cell priming and activation. Accordingly, combining MEK inhibitors (MEKi) with agonist antibodies (Abs) targeting the immunostimulatory CD40 receptor results in potent synergistic antitumor efficacy. Detailed analysis of the mechanism of action of MEKi shows that this drug exerts multiple pro-immunogenic effects, including the suppression of M2-type macrophages, myeloid derived suppressor cells and T-regulatory cells. The combination of MEK inhibition with agonist anti-CD40 Ab is therefore a promising therapeutic concept, especially for the treatment of mutant Kras-driven tumors such as pancreatic ductal adenocarcinoma. | ||
| 700 | 1 | |a Hägele, Tanja |d 1991- |e VerfasserIn |0 (DE-588)1213369878 |0 (DE-627)1713914751 |4 aut | |
| 700 | 1 | |a Mochayedi, Julian |d 1988- |e VerfasserIn |0 (DE-588)1213370205 |0 (DE-627)1713915170 |4 aut | |
| 700 | 1 | |a Drebant, Jennifer |e VerfasserIn |0 (DE-588)121337037X |0 (DE-627)1713915480 |4 aut | |
| 700 | 1 | |a Vent, Caroline |e VerfasserIn |4 aut | |
| 700 | 1 | |a Blobner, Sven |e VerfasserIn |4 aut | |
| 700 | 1 | |a Noll, Julia Han |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nickel, Irena |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schumacher, Corinna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Boos, Sophie Luise |e VerfasserIn |4 aut | |
| 700 | 1 | |a Daniel, Aline Sophie |e VerfasserIn |0 (DE-588)1213371686 |0 (DE-627)1713920212 |4 aut | |
| 700 | 1 | |a Wendler, Susann |e VerfasserIn |0 (DE-588)1124103015 |0 (DE-627)877825734 |0 (DE-576)482303093 |4 aut | |
| 700 | 1 | |a Volkmar, Michael |d 1976- |e VerfasserIn |0 (DE-588)143064592 |0 (DE-627)704379457 |0 (DE-576)334850193 |4 aut | |
| 700 | 1 | |a Strobel, Oliver |d 1974- |e VerfasserIn |0 (DE-588)123658977 |0 (DE-627)706385101 |0 (DE-576)293812357 |4 aut | |
| 700 | 1 | |a Offringa, Rienk |e VerfasserIn |0 (DE-588)1066807485 |0 (DE-627)817963391 |0 (DE-576)426161424 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature Communications |d [London] : Springer Nature, 2010 |g 11(2020) Artikel-Nummer 2176, 18 Seiten |h Online-Ressource |w (DE-627)626457688 |w (DE-600)2553671-0 |w (DE-576)331555905 |x 2041-1723 |7 nnas |a Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy |
| 773 | 1 | 8 | |g volume:11 |g year:2020 |g extent:18 |a Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41467-020-15979-2 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41467-020-15979-2 |x Verlag |
| 951 | |a AR | ||
| 992 | |a 20200708 | ||
| 994 | |a 2020 | ||
| 998 | |g 1066807485 |a Offringa, Rienk |m 1066807485:Offringa, Rienk |d 910000 |d 910200 |e 910000PO1066807485 |e 910200PO1066807485 |k 0/910000/ |k 1/910000/910200/ |p 15 |y j | ||
| 998 | |g 123658977 |a Strobel, Oliver |m 123658977:Strobel, Oliver |d 910000 |d 910200 |e 910000PS123658977 |e 910200PS123658977 |k 0/910000/ |k 1/910000/910200/ |p 14 | ||
| 998 | |g 143064592 |a Volkmar, Michael |m 143064592:Volkmar, Michael |d 50000 |e 50000PV143064592 |k 0/50000/ |p 13 | ||
| 998 | |g 1124103015 |a Wendler, Susann |m 1124103015:Wendler, Susann |p 12 | ||
| 998 | |g 1213371686 |a Daniel, Aline Sophie |m 1213371686:Daniel, Aline Sophie |p 11 | ||
| 998 | |g 121337037X |a Drebant, Jennifer |m 121337037X:Drebant, Jennifer |p 4 | ||
| 998 | |g 1213370205 |a Mochayedi, Julian |m 1213370205:Mochayedi, Julian |d 140000 |e 140000PM1213370205 |k 0/140000/ |p 3 | ||
| 998 | |g 1213369878 |a Hägele, Tanja |m 1213369878:Hägele, Tanja |p 2 | ||
| 998 | |g 1186002131 |a Baumann, Daniel |m 1186002131:Baumann, Daniel |d 910000 |d 910200 |e 910000PB1186002131 |e 910200PB1186002131 |k 0/910000/ |k 1/910000/910200/ |p 1 |x j | ||
| 999 | |a KXP-PPN1713927888 |e 3711417604 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"recId":"1713927888","id":{"eki":["1713927888"],"doi":["10.1038/s41467-020-15979-2"]},"origin":[{"dateIssuedKey":"2020","dateIssuedDisp":"01 May 2020"}],"relHost":[{"title":[{"title":"Nature Communications","title_sort":"Nature Communications"}],"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"note":["Gesehen am 13.06.24"],"origin":[{"publisher":"Springer Nature ; Nature Publishing Group UK","publisherPlace":"[London] ; [London]","dateIssuedDisp":"[2010]-"}],"id":{"issn":["2041-1723"],"zdb":["2553671-0"],"eki":["626457688"]},"disp":"Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapyNature Communications","part":{"volume":"11","extent":"18","year":"2020","text":"11(2020) Artikel-Nummer 2176, 18 Seiten"},"pubHistory":["2010-"],"type":{"bibl":"periodical","media":"Online-Ressource"},"recId":"626457688"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"person":[{"role":"aut","family":"Baumann","display":"Baumann, Daniel","given":"Daniel"},{"family":"Hägele","display":"Hägele, Tanja","role":"aut","given":"Tanja"},{"given":"Julian","family":"Mochayedi","display":"Mochayedi, Julian","role":"aut"},{"given":"Jennifer","family":"Drebant","display":"Drebant, Jennifer","role":"aut"},{"role":"aut","display":"Vent, Caroline","family":"Vent","given":"Caroline"},{"role":"aut","display":"Blobner, Sven","family":"Blobner","given":"Sven"},{"role":"aut","family":"Noll","display":"Noll, Julia Han","given":"Julia Han"},{"role":"aut","family":"Nickel","display":"Nickel, Irena","given":"Irena"},{"given":"Corinna","role":"aut","family":"Schumacher","display":"Schumacher, Corinna"},{"display":"Boos, Sophie Luise","family":"Boos","role":"aut","given":"Sophie Luise"},{"family":"Daniel","display":"Daniel, Aline Sophie","role":"aut","given":"Aline Sophie"},{"given":"Susann","display":"Wendler, Susann","family":"Wendler","role":"aut"},{"role":"aut","family":"Volkmar","display":"Volkmar, Michael","given":"Michael"},{"display":"Strobel, Oliver","family":"Strobel","role":"aut","given":"Oliver"},{"role":"aut","family":"Offringa","display":"Offringa, Rienk","given":"Rienk"}],"name":{"displayForm":["Daniel Baumann, Tanja Hägele, Julian Mochayedi, Jennifer Drebant, Caroline Vent, Sven Blobner, Julia Han Noll, Irena Nickel, Corinna Schumacher, Sophie Luise Boos, Aline Sophie Daniel, Susann Wendler, Michael Volkmar, Oliver Strobel, Rienk Offringa"]},"note":["Gesehen am 08.07.2020"],"title":[{"title_sort":"Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy","title":"Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy"}],"language":["eng"],"physDesc":[{"extent":"18 S."}]} | ||
| SRT | |a BAUMANNDANPROIMMUNOG0120 | ||