TY  - JOUR
AU  - Sadik, Ahmed
AU  - Somarribas Patterson, Luis F
AU  - Öztürk, Selcen
AU  - Mohapatra, Soumya R
AU  - Panitz, Verena
AU  - Secker, Philipp F
AU  - Pfänder, Pauline
AU  - Loth, Stefanie
AU  - Salem, Heba
AU  - Prentzell, Mirja Tamara
AU  - Berdel, Bianca
AU  - Iskar, Murat
AU  - Faessler, Erik
AU  - Reuter, Friederike
AU  - Kirst, Isabelle
AU  - Kalter, Verena
AU  - Foerster, Kathrin I
AU  - Jäger, Evelyn
AU  - Guevara, Carina Ramallo
AU  - Sobeh, Mansour
AU  - Hielscher, Thomas
AU  - Poschet, Gernot
AU  - Reinhardt, Annekathrin
AU  - Hassel, Jessica C
AU  - Zapatka, Marc
AU  - Hahn, Udo
AU  - von Deimling, Andreas
AU  - Hopf, Carsten
AU  - Schlichting, Rita
AU  - Escher, Beate I
AU  - Burhenne, Jürgen
AU  - Haefeli, Walter E
AU  - Ishaque, Naveed
AU  - Böhme, Alexander
AU  - Schäuble, Sascha
AU  - Thedieck, Kathrin
AU  - Trump, Saskia
AU  - Seiffert, Martina
AU  - Opitz, Christiane
TI  - IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
JO  - Cell
VL  - 182
IS  - 5
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2020-01707
SP  - 1252-1270.e34
PY  - 2020
N1  - 2020 Sep 3;182(5):1252-1270.e34#EA:B350#LA:B350#
AB  - Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded systematic investigation of AHR activity and its upstream enzymes across human cancers. A pan-tissue AHR signature, derived by natural language processing, revealed that across 32 tumor entities, interleukin-4-induced-1 (IL4I1) associates more frequently with AHR activity than IDO1 or TDO2, hitherto recognized as the main Trp-catabolic enzymes. IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. It associates with reduced survival in glioma patients, promotes cancer cell motility, and suppresses adaptive immunity, thereby enhancing the progression of chronic lymphocytic leukemia (CLL) in mice. Immune checkpoint blockade (ICB) induces IDO1 and IL4I1. As IDO1 inhibitors do not block IL4I1, IL4I1 may explain the failure of clinical studies combining ICB with IDO1 inhibition. Taken together, IL4I1 blockade opens new avenues for cancer therapy.
LB  - PUB:(DE-HGF)16
C6  - pmid:32818467
DO  - DOI:10.1016/j.cell.2020.07.038
UR  - https://inrepo02.dkfz.de/record/157610
ER  -