High indoleamine 2,3-dioxygenase transcript levels predict better outcome after front-line cancer immunotherapy

Yu Fujiwara, Shumei Kato, Daisuke Nishizaki, Hirotaka Miyashita, Suzanna Lee, Mary K. Nesline, Jeffrey M. Conroy, Paul DePietro, Sarabjot Pabla, Scott M. Lippman, Razelle Kurzrock

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1), which catabolizes tryptophan, is a potential target to unlock the immunosuppressive tumor microenvironment. Correlations between IDO1 and immune checkpoint inhibitor (ICI) efficacy remain unclear. Herein, we investigated IDO1 transcript expression across cancers and clinical outcome correlations. High IDO1 transcripts were more frequent in uterine (54.2%) and ovarian cancer (37.2%) but varied between and within malignancies. High IDO1 RNA expression was associated with high expression of PD-L1 (immune checkpoint ligand), CXCL10 (an effector T cell recruitment chemokine), and STAT1 (a component of the JAK-STAT pathway) (all multivariable p < 0.05). PIK3CA and CTCF alterations were more frequent in the high IDO1 group. High IDO1 expression was an independent predictor of progression-free survival (adjusted HR = 0.44, 95% CI 0.20–0.99, p = 0.049) and overall survival (adjusted HR = 0.31, 95% CI 0.11–0.87, p = 0.026) after front-line ICIs. IDO1 expression warrants further exploration as a predictive biomarker for immunotherapy. Moreover, co-expressed immunoregulatory molecules merit exploration for co-targeting.

Original languageEnglish
Article number109632
JournaliScience
Volume27
Issue number4
DOIs
StatePublished - 19 Apr 2024

Keywords

  • Cancer
  • Immunology
  • Molecular biology

Fingerprint

Dive into the research topics of 'High indoleamine 2,3-dioxygenase transcript levels predict better outcome after front-line cancer immunotherapy'. Together they form a unique fingerprint.

Cite this