IDO1 Expression Increased After Neoadjuvant Therapy Predicts Poor Pathologic Response and Prognosis in Esophageal Squamous Cell Carcinoma

Abstract

Indoleamine 2,3-dioxygenase (IDO1) plays an important role in tumor immune evasion. In this study, we investigated the changes of tumor IDO1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) status in tumor microenvironment (TME) after neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) in esophageal squamous cell carcinoma (ESCC), respectively. Moreover, the potential predictive value of the changes of tumor IDO1 expression and CD8+TILs status on pathologic response and clinical outcome was further evaluated. By matching propensity scores in 295 patients, a total of 85 ESCC patients with neoadjuvant therapy followed by surgery were recruited, including 17 patients with NCRT and 68 patients with NCT. Tumor IDO1 expression and CD8+TILs within TME in paired specimens were evaluated by immunohistochemistry, and the changes of tumor IDO1 expression and CD8+TILs between the paired specimens were estimated. Tumor IDO1 expression significantly increased from baseline to postoperative tumor tissue after NCT ( p = 0.002), whereas no significant difference was detected after NCRT ( p = 0.44). The density of CD8+TILs in the tumor-invasive margin increased significantly after neoadjuvant therapy, and there was no significant difference in density changes of CD8+TILs between the NCRT and NCT groups ( p = 0.118). Upregulation of tumor IDO1 expression after neoadjuvant therapy was associated with poor pathologic response ( p = 0.002). Lastly, multivariate Cox analysis showed that IDO1-rise patients after neoadjuvant therapy were related to poor prognosis ( p = 0.047). These results indicated that chemotherapy could promote tumor IDO1 expression, and the increased tumor IDO1 expression after neoadjuvant therapy predicted poor pathologic response and prognosis in ESCC.

Construction of a novel necroptosis-related lncRNA signature for prognosis prediction in esophageal cancer

“…PD(L)1 inhibitors are increasingly used after first-line therapies in EC, especially among patients initially receiving chemotherapy [ 45 , 46 ]. IDO1 expression is associated with an unfavorable clinical outcome in EC, supporting its role as a prognostic biomarker [ 47 , 48 ]. Finally, the prediction of potential therapeutic drugs showed 14 compounds in the high-risk group and 2 compounds in the low-risk group had a higher sensitivity, which provided a good strategy for clinical treatment of EC patients.…”

Tumor Microenvironment Characterization in Breast Cancer Identifies Prognostic and Neoadjuvant Chemotherapy Relevant Signatures

“…Recently, many studies focused on biomarkers that were highly associated with treatment responses such as chemotherapy ( Lee et al, 2019 ; Al Amri et al, 2020 ; Jiao et al, 2020 ; Valdés-Ferrada et al, 2020 ; Zhao et al, 2020 ), and most of them focused on signatures of genes, microRNAs, lncRNAs, and epigenetic biomarkers for the prediction of long-term survival in patients with tumor. However, these signatures cannot be widely used in clinic because of the variability in gene sequencing methods, the inconvenience in the use of assay platforms, and the requirement for specialized analyses.…”

The Role of Indoleamine 2, 3-Dioxygenase 1 in Regulating Tumor Microenvironment

“…Friberget et al first reported the IDO1 pathway as a possible tumor immune escape mechanism in 2002 when they observed IDO1 expression by monocytes in tumor tissues and tumor-draining lymph nodes [ 67 ]. In the past decade, numerous studies have observed high IDO1 levels in human tumors, including glioblastoma, head and neck squamous cell carcinoma, breast cancer adrenocortical carcinoma, esophageal squamous cell carcinoma, gastric cancer, and colon cancer [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ].…”

“…The IDO1 level is associated with the histological malignant grade and adverse prognosis. Jiao et al observed increasing IDO1 expression in TME after neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy accompanied by poor pathological response and prognosis [ 70 ]. IDO1 pathway accelerates colorectal cancer growth, local invasion and suppresses CD8 + T cell response.…”