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

doi:10.1016/j.isci.2024.109632

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

iScience. 2024 Mar 28;27(4):109632. doi: 10.1016/j.isci.2024.109632. eCollection 2024 Apr 19.

Authors

Affiliations

¹ Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
² Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY 10003, USA.
³ Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA 92093, USA.
⁴ Division of Hematology and Oncology, Dartmouth Cancer Center. One Medical Center Drive, Lebanon, NH 03766, USA.
⁵ OmniSeq (Labcorp Oncology), Buffalo, NY 14203, USA.
⁶ MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

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.

Keywords: Cancer; Immunology; Molecular biology.

Abstract

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