Abstract C42: Development and validation of an IHC-based detection method for studying indoleamine 2,3-dioxygenase 1 (IDO1) expression in human cancers.

Abstract

Abstract Indoleamine 2,3-dioxygenase-1 (IDO1) mediates oxidative cleavage of tryptophan, an amino acid essential for cell proliferation and survival. The depletion of tryptophan and the generation of tryptophan metabolites have been demonstrated to be an important regulator of immune function. IDO1 is induced by interferons and TLR agonists and is expressed in a wide variety of human cancers as well as in the tumor-draining lymph nodes. High IDO1 expression is significantly associated with more rapid disease progression and poor prognosis in multiple cancer types. Numerous studies have shown that IDO1 negatively regulates immune functions via several potential cellular mechanisms, which in turn allows tumor escape from host immune surveillance. Therefore, inhibition of IDO1 may have therapeutic potential in cancer and IDO1 expression may serve as a selective marker of a responsive population. INCB024360, a novel IDO1-selective inhibitor, is currently being evaluated in clinical trials of cancer patients. To support the clinical development of INCB024360, we have developed and validated an immunohistochemistry (IHC)-based method using rabbit polyclonal antisera that specifically detects IDO1 protein expression. The method has been used to determine IDO1 expression in primary biopsies from patients studied in INCB024360 clinical trials. The method can be used to determine the prevalence of IDO1 expression in a variety of human cancers, identify histologic subtypes that might be associated with IDO1 expression and examine IDO1 coexpression with other immune modifying pathways. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C42. Citation Format: Xiangdong Liu, Gengjie Yang, Alexander Margulis, Rich Wynn, Peggy Scherle, Robert Newton. Development and validation of an IHC-based detection method for studying indoleamine 2,3-dioxygenase 1 (IDO1) expression in human cancers. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C42.