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
Affiliations
Yu Fujiwara
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; Corresponding author
Shumei Kato
Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA 92093, USA; Corresponding author
Daisuke Nishizaki
Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
Hirotaka Miyashita
Division of Hematology and Oncology, Dartmouth Cancer Center. One Medical Center Drive, Lebanon, NH 03766, USA
Suzanna Lee
Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
Mary K. Nesline
OmniSeq (Labcorp Oncology), Buffalo, NY 14203, USA
Jeffrey M. Conroy
OmniSeq (Labcorp Oncology), Buffalo, NY 14203, USA
Paul DePietro
OmniSeq (Labcorp Oncology), Buffalo, NY 14203, USA
Sarabjot Pabla
OmniSeq (Labcorp Oncology), Buffalo, NY 14203, USA
Scott M. Lippman
Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
Razelle Kurzrock
MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Corresponding author
Summary: 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.
