Fujiwara Yu, Kato Shumei, Nishizaki Daisuke, Miyashita Hirotaka, Lee Suzanna, Nesline Mary K, Conroy Jeffrey M, DePietro Paul, Pabla Sarabjot, Lippman Scott M, Kurzrock Razelle
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY 10003, USA.
iScience. 2024 Mar 28;27(4):109632. doi: 10.1016/j.isci.2024.109632. eCollection 2024 Apr 19.
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 < 0.05). and 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, = 0.049) and overall survival (adjusted HR = 0.31, 95% CI 0.11-0.87, = 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.
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