Cell: Discover the new metabolic immuno checkpoint IL4I1! It activates aromatic hydrocarbons and promotes tumor progress.

Aug 26, 2020 /--- In a new study, researchers from the German Cancer Research Center (DKFZ) and the Berlin Institute of Health (BIH) found that the metabolic enzyme IL4I1 (Interleukin-4-Induced-1) promotes the spread of tumor cells and suppresses the immune system.
the enzyme that activates dioxin receptors is produced in large numbers by tumor cells.
the future, inhibiting IL4I1 could open up new opportunities for cancer treatment.
results were published online August 19, 2020 in the journal Cell under the title "IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progress."
author of the paper is Christiane Opitz of the German Cancer Research Centre.
first authors of the paper were Ahmed Sadik, Luis F. Somarribas Patterson, Selcen ?ztürk and Soumya R. Mohapatra of the German Cancer Research Centre.
from Cell, 2020, doi:10.1016/j.cell.2020.07.038.
can activate the body's own defenses against cancer and is revolutionized in cancer treatment.
, despite some breakthrough success, only a few patients can benefit from current drugs.
the new study, the authors looked at the molecular mechanisms by which tumors escape the destruction of the immune system.
their findings may provide important information for the development of new immunotherapy concepts.
aryl hydrocarbon receptor (AHR) is also known as a diexin receptor because of its toxic effects.
, not only toxins, but also the body's own metabolites activate the subject.
example is the degradation of the amino acid tryptophan, which we take from food as a component of protein.
these metabolites to their own service: they promote the mobility of cancer cells and weaken the immune response to tumors.
, however, the metabolic pathways produced by related tryptophan degradation products have not been fully studied.
to learn more about which tryptophan degradation enzymes were systematically studied in 32 different types of cancers, the authors said.
one molecule that caught their particular attention: the enzyme IL4I1.
No other tryptophan metabolase is as closely associated with the activation of deoxin receptors as IL4I1: "The metabolites formed by IL4I1 bind to and activate it, causing immune cells to be inhibited," explains Saskia Trump of the Berlin Institute of Health.
clinically noteworthy is the observed decrease in the probability of survival in patients with gliomas, a malignant brain tumor, and the decrease in the probability of survival in patients with higher concentrations of this enzyme in these tumors.
in mouse models of chronic lymphatic leukemia (CLL), a type of blood cancer, IL4I1 has been shown to promote cancer by affecting the immune system.
Seiffert explained, "In animals that do not produce IL4I1 in the tumor environment due to genetic changes, the immune system has a significantly higher success rate in preventing cancer progressity."
," Opitz said, "IL4I1 has great potential as a drug target."
so far, drugs that inhibit tryptophan metabolase have failed in clinical trials because tumors do not respond to them.
, the role of IL4I1 has so far been neglected, and the enzyme has not yet been tested as a target molecule.
" (bioon.com) Reference: 1. Ahmed Sadik et al, IL4I1 Is a Metabolic Immune Checkpoint that Activates AHR and Promotes Tumor Progression. Cell, 2020, doi:10.1016/j.cell.2020.07.038.2.A metabolic enzyme as a potential new target for cancer immune therapies.