Abstract 4061: Investigating the Indoleamine 2,3-dioxygenase 1 (IDO1) responsive gene expression panel in predicting outcome in stage matched colorectal cancer patients

Abstract

Colorectal cancer has emerged as a third most commonly diagnosed cancer in males and second in females. There is need for new tools in the form of prognostic biomarkers which could assist in tailoring of individualized treatment. Indoleamine 2,3-dioxygenase (IDO), a single chain oxido-reductase that serves as a catalyst for the degradation of tryptophan into kynurenine, has merged as a key player in T-cell suppression and in the induction of immune tolerance to tumors. IDO inhibitors have entered the clinical arena with a promise to restore immune functions in breast cancer patients. We identified through extensive literature search a list of IDO1-responsive genes. These gene along with IDO1 interferes with cancer control pathways and leads to cancer progression. The expression of following genes was quantified on Nanostring platform - IDO1, CTLA4, IL4R, PDL1, CTLA4, IL4R, HIF and IL6. Under an approved IRB protocol we identified 750 colon cancer patients at the Georgia Cancer Center with a 5 year follow-up. These patients were then divided into different experimental groups based on tumor stage (AJCC stages 1-4), survival (more or less than 3 years), tumor grade (AJCC grades 1-3), and age (older or younger than 68). A total of 88 patients fitted in our inclusion criteria on the basis of survival duration after diagnosis. The FFPE blocks were acquired from Medical College of Georgia, Augusta. Total RNA was isolated and quantified through Nanodrop method. The statistical analysis of data was performed using student t-test and Pearson correlation. IDO1 had significantly expressed at higher levels in stage IV patients (p = 0.01*). CTLA4 and IL4R were significantly expressed in stage IV patients with higher survival (p = 0.03*) and (p = 0.04*) respectively. PDL1 expression was higher in stage III patients with higher survival (p = 0.04*). CTLA4 was expressed at higher levels in patients with higher survival (>5 years). IDO1 was expressed at higher levels in males (p = 0.23*). In smokers, HIF and IL6 expression was higher as compared to non-smokers, (p = 0.02*). Preclinical data have shown that IDO1 inhibitors such as 1-Methyl-D-Tryptophan (1-MT) can synergize with chemotherapy in killing tumors. Therefore the inhibition of IDO as an approach to immunotherapy has a high amount of potential. Combining this new agent with current therapies may boost their efficacy and improve survival in TNBC patients. Furthermore, despite the rapid progress made in cancer immunotherapy, very few biomarkers are available for predicting the responsiveness and effectiveness of immunotherapy agents. Therefore, there is an urgent need to identify and develop such predictive biomarkers. These findings points to the clinical significance of IDO responsive genes and tested its importance in a gene expression based prognostic biomarker panel in CRC patients. Citation Format: Ravindra Kolhe, Chance Bloomer, Pankaj Ahluwalia, Chetan Pundkar, Saleh Heneidi, Ashis Mondal. Investigating the Indoleamine 2,3-dioxygenase 1 (IDO1) responsive gene expression panel in predicting outcome in stage matched colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4061.