Integrated analyses reveal IDO1 as a prognostic biomarker coexpressed with PD-1 on tumor-associated macrophages in esophageal squamous cell carcinoma
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Le résumé fourni par la source
Background: Inhibition of indolamine-2,3-dioxygenase 1 (IDO1) has been proposed as a promising strategy for cancer immunotherapy; however, it has failed in clinical trials. Macrophages in the tumor microenvironment (TME) contribute to immune escape and serve as potential therapeutic targets. This study investigated the expression pattern of IDO1 in TME and its impact on prognosis and therapeutic response of patients with esophageal squamous cell carcinoma (ESCC). Methods: RNA sequencing data from 95 patients with ESCC from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic value of IDO1. Bioinformatics tools were used to estimate scores for stromal and immune cells in tumour tissues, abundance of eight immune cell types in TME, and sensitivity of chemotherapeutic drugs and immune checkpoint (IC) blockage. The results were validated using digitalized immunohistochemistry and multiplexed immunofluorescence in ESCC tissue samples obtained from our clinical center. Results: TCGA and validation data suggested that high expression of IDO1 was associated with poor patient survival, and IDO1 was an independent prognostic factor. IDO1 expression positively correlated with macrophages in TME and PDCD1 within diverse IC genes. Single-cell RNA sequencing data analysis and multiplexed immunofluorescence verified the coexpression of IDO1 and PD-1 in tumor-associated macrophages (TAMs). Patients with high IDO1 expression showed increased sensitivity to various chemotherapeutic drugs, while were more likely to resist IC blockage. Conclusion: This study identifies IDO1 as an independent prognostic indicator of OS in patients with ESCC, reveals a compelling connection of IDO1, PD-1, and TAMs, and explores the sensitivity of patients with high IDO1 expression to chemotherapeutic drugs and their resistance to IC blockade. These findings open new avenues for potential targets in ESCC immunotherapy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Integrated analyses reveal IDO1 as a prognostic biomarker coexpressed with PD-1 on tumor-associated macrophages in esophageal squamous cell carcinoma
- Date Crossref
- 16/09/2024
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Chinese PLA General Hospital pays non établi dans la noticeÉtablissement de santé
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Chinese People's Liberation Army Department of Basic Medicine pays non établi dans la noticeOrganisme public
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Tianjin Fourth Hospital pays non établi dans la noticeÉtablissement de santé
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Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer pays non établi dans la noticeÉtablissement de santé
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Tianjin Fourth Center Hospital Department of Cardiothoracic Surgery pays non établi dans la noticeÉtablissement de santé
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Tianjin Cancer Hospital Airport Free Trade Zone Hospital Department of Oncology Surgery pays non établi dans la noticeÉtablissement de santé
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Chinese PLA General Hospital, Department of Basic Medicine — Chinese People's Liberation Army et Tianjin Fourth Hospital, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.