Indoleamine 2,3-dioxygenase expression and overall survival in patients diagnosed with breast cancer in Pakistan

Abstract

BackgroundImmune dysfunction in breast cancer patients is well established. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is linked with progression of cancer. IDO is overexpressed in triple-negative breast cancer (TNBC) cases.Materials and methodsWe conducted the first study to analyze IDO expression and overall survival in breast cancer cases in Pakistan. Expression of IDO, estrogen receptor (ER), progesterone receptor (PR), and human EGF receptor 2 (HER2) was evaluated by immunohistochemistry. Formalin-fixed paraffin-embedded breast cancer tissues of 100 (TNBC, n=49 and non-TNBC, n=51) patients were obtained from Shaukat Khanum Memorial Cancer Hospital and Research Centre. IDO expression was analyzed in association with clinicopathological features and overall survival. A total of 100 patients were classified based on the ordinal IDO score variables as low, medium, and high. In addition, overall mean age and SD of patients was 48.28±11.82.ResultsImmunohistochemical analysis showed that high IDO was observed in the TNBC patients (65.3%) compared to that in the non-TNBC patients (33.3%). Multivariable analyses showed that TNBC was an independent risk factor for high IDO expression. Overall survival was also significantly associated with IDO score.ConclusionOur study showed that IDO protein expression is higher in TNBC patients (P<0.01) and may suggest its role in disease pathogenesis. TNBC might be effectively treated with IDO inhibitors. Furthermore, high IDO expression is considerably associated with overall decreased patient survival. IDO might be utilized as a potential biomarker and immunotherapeutic target in breast cancer patients.

Forkhead box P3 and indoleamine 2,3-dioxygenase co-expression in Pakistani triple negative breast cancer patients

“…IDO expression is also associated with TNBC[ 26 ]. Previously we showed high IDO expression in TNBC patients from Pakistan[ 35 ]. The aim of our current study was to identify the substantial association between FOXP3-positive T-regs and IDO in TNBC patients.…”

The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

“…Expression of high levels of IDO by cancer cells has been correlated with poor prognosis and reduced overall survival in patients with solid tumors including, breast cancer [140]. In fact, microvesicles released by malignant tumors, in breast cancer patients contained a significantly high expression of IDO compared to normal breast tissues or benign tumor samples [148,149]. In addition, IDO expression is higher in advanced stages of breast cancer and mainly expressed in the TNBC subgroup [148,149].…”

“…In fact, microvesicles released by malignant tumors, in breast cancer patients contained a significantly high expression of IDO compared to normal breast tissues or benign tumor samples [148,149]. In addition, IDO expression is higher in advanced stages of breast cancer and mainly expressed in the TNBC subgroup [148,149]. The expression of IDO in TNBC has also shown to correlate with high expressions of PD-L1 in invasive primary breast carcinomas which highlights the need for combination therapies over single ones [150].…”

Association between Cyclooxygenase-2 and Indoleamine 2,3-Dioxygenase Expression in Breast Cancer Patients from Pakistan

“…IDO expression is involved in breast tumor growth and pulmonary metastasis (Levina et al, 2012). Furthermore, high IDO expression is significantly linked with overall decreased patient survival (Asghar et al, 2019). COX-2 and IDO promote breast cancer progression (Chen et al, 2014).…”

“…DAB 3, 3'-diaminobenzidine tetrahydrochloride hydrate was used as chromogen. Slides were dehydrated and cover slipped as per our earlier described laboratory protocol (Asghar et al, 2019). Slides were visualized by an optical microscope (Provis AX-70, Olympus, Melville, NY).…”