Genetic Evidence Identified for Role of IDO in Tumorigenesis
IL-6 down, impaired myeloid-derived suppressor cells in indoleamine 2,3-dioxygenase-deficient mice
MONDAY, July 23 (HealthDay News) -- Mice deficient in indoleamine 2,3-dioxygenase (IDO) have reduced tumor burden and improved survival, with greatly attenuated interleukin-6 (IL-6) and impaired protumorigenic myeloid-derived suppressor cells (MDSC) seen in conjunction with the loss of IDO, according to a study published online July 19 in Cancer Discovery.
Courtney Smith, Ph.D., from the Lankenau Institute for Medical Research in Wynnewood, Penn., and colleagues generated mice deficient in IDO to examine the role of the enzyme in mouse models of lung cancer and breast cancer-derived lung metastasis.
The researchers found that IDO-deficient mice had smaller lung cancers and improved survival. Micro-computed tomography imaging showed reduced density of the underlying pulmonary blood vessels. Both tumor models also had greatly reduced production of IL-6, which resulted in impairment of protumorigenic MDSC.
"This study provides preclinical, genetic proof-of-concept that the immunoregulatory enzyme IDO contributes to autochthonous carcinoma progression and to the creation of a metastatic niche," Smith and colleagues conclude. "IDO deficiency in vivo negatively impacted both vascularization and IL-6-dependent, MDSC-driven immune escape, establishing IDO as an overarching factor directing the establishment of a protumorigenic environment."
One author is an employee of NewLink Genetics Corporation; several authors disclosed financial and consulting ties to NewLink.