Off-tumor IDO1 target engagements determine the cancer-immune set point and predict the immunotherapeutic efficacy.

ABSTRACT:

Background

Indoleamine-2,3-dioxygenase 1 (IDO1) has been intensively pursued as a therapeutic target to reverse the immunosuppressive cancer-immune milieu and promote tumor elimination. However, recent failures of phase III clinical trials with IDO1 inhibitors involved in cancer immunotherapies highlight the urgent need to develop appropriate methods for tracking IDO1 when the cancer-immune milieu is therapeutically modified.

Methods

We utilized a small-molecule radiotracer, ¹¹C-l-1MTrp, to quantitatively and longitudinally visualize whole-body IDO1 dynamics. Specifically, we first assessed ¹¹C-l-1MTrp in mice-bearing contralateral human tumors with distinct IDO1 expression patterns. Then, we applied ¹¹C-l-1MTrp to longitudinally monitor whol

SUBMITTER: Xie L 

PROVIDER: S-EPMC8237741 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature