Analysis of Expression and Activity of Indoleamine 2,3- dioxygenase in Breast Cancer Patients from Pakistan

Abstract

Modulation of immune system is associated with development and progression of cancers. Owing to the complexity of tumor formation, involving various genetic, epigenetic and environmental factors; immune system generates varied responses under different circumstances. A shift in balance from pro-inflammatory factors and towards immune tolerance promoting factors leads a patient towards poor prognosis and reduces the chances of cancer-free survival. Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme which is involved in suppression of effector T-cell responses by catabolizing essential amino acid tryptophan. Involvement of IDO in breast cancer is critical to understand the significance of immune system in breast cancer development and progression. Here, we conducted the first study to analyze IDO expression and its enzymatic activity in breast cancer cases from Pakistan Paraffin fixed formalin embedded (PFFE) breast cancer biopsies were obtained from one hundred (100) patients from Pakistan. Expression of IDO in breast cancer biopsies was examined through immunohistochemistry (IHC). Clinicopathological characteristics of patients like age at onset of breast cancer, tumor size, histology of tumor, tumor grade, and metastasis of cancer, expression of estrogen, progesterone and human epithelial growth factor receptor were compared with IDO expression. Activity of IDO was analyzed through colorimetric assay in plasma samples of fifteen (15) breast cancer patients. It was compared with fifteen (15) healthy controls. IDO was over-expressed in majority of breast cancer patients. Triple negative breast cancers had significantly higher expression of IDO as compared to non- triple negative breast cancers (p<0.01). Overall survival of breast cancer patients with higher expression of IDO was decreased (p=0.04). IDO enzymatic activity was also higher in breast cancer patients as compared to controls (p<0.0001). IDO might be associated with prognosis of triple negative breast cancer patients and its role in modulation of immune system in breast cancer needs to be explored.