Journal of Translational Medicine最新文献

Background: Epidermal growth factor (EGF) and its receptor EGF(EGFR) play crucial roles in glioblastoma (GBM) prognosis. However, non-invasive assessment of their expression remains challenging. This study aimed to determine whether radiomics features extracted from contrast-enhanced MRI could predict EGFR expression in high-grade gliomas (HGG) and to explore their associations with immune infiltration and therapeutic response of EGFR-Targeted antibody drug conjugates(EGFR-ADCs).

Methods: We extracted radiomic features from contrast-enhanced MRI of 298 GBM patients from The Cancer Imaging Archive (TCIA) and matched them with RNA-seq data from The Cancer Genome Atlas (TCGA). Feature selection was performed using minimum redundancy maximum relevance (mRMR) and recursive feature elimination (RFE). Machine learning models were built to predict EGF/EGFR expression. Radiogenomic associations were validated by immune infiltration analysis. Patient-Derived Tumor-Like Cell Clusters (PTC) were used to compare the antitumor efficacy of EGFR- ADCs and temozolomide.

Results: Elevated EGF/EGFR expression correlated with poor prognosis and increased infiltration of M2 macrophages, regulatory T cells, and CD4⁺ memory T cells. Pathway analysis demonstrated significant enrichment of the mechanistic target of rapamycin (mTOR) and Mitogen-Activated Protein Kinase (MAPK) signaling cascades. Radiomics-based prediction models achieved robust performance (AUC > 0.85) in stratifying EGFR expression status. In EGFR-positive tumor tissues, EGFR-ADCs exerted antitumor efficacy similar to that of temozolomide.

Conclusions: EGF/EGFR expression is associated with immunosuppressive microenvironments and adverse outcomes in HGG. Radiomics may provide a non-invasive approach for estimating EGFR expression, although model performance requires external validation and EGFR-ADCs showed partial inhibitory activity within the tested range, though potency remains to be defined.These findings suggest a framework into radiogenomic stratification and targeted therapy in GBM.

Background: Tryptophan metabolism is essential for immune homeostasis, neurological function regulation, and tumor microenvironment modulation. The indoleamine 2,3-dioxygenase (IDO) family, including IDO1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), serves as the rate-limiting enzymes in the kynurenine pathway of tryptophan catabolism. These enzymes act as a critical molecular hub linking immune metabolism, neural regulation, and tumorigenesis, and their aberrant activity is closely associated with the pathogenesis of various diseases such as tumors, autoimmune disorders, infectious diseases, and neurological conditions. Although IDO family inhibitors have shown potential in cancer immunotherapy, clinical trial results remain controversial, highlighting the complexity of their mechanisms and the need for systematic summarization of relevant research progress.

Main body: This review first elaborates on the structural characteristics, tissue distribution, catalytic efficiency, and core biological functions of IDO1, IDO2, and TDO2, emphasizing their distinct and complementary roles in tryptophan metabolism and immune regulation. It then systematically summarizes the regulatory mechanisms of the IDO family at transcriptional, translational, and post-translational levels. Subsequently, the review details the roles of each family member in different disease contexts: IDO1 predominantly mediates local immunosuppression and tumor immune escape; IDO2 drives B cell-related inflammation and autoimmune responses; TDO2 maintains systemic tryptophan homeostasis and links neurometabolism to immunity. Additionally, the article comprehensively discusses current therapeutic strategies targeting the IDO family, including small-molecule inhibitors (single-target, dual-target, and multi-target), peptide vaccines, and nano-delivery systems, while analyzing the challenges faced in clinical translation, such as pathway compensation, insufficient patient stratification, and off-target effects.

Conclusions: The IDO family plays a multifaceted and context-dependent role in various diseases through the kynurenine pathway, making it a promising target for diagnostic biomarkers and therapeutic intervention. Future research should focus on optimizing multi-target inhibitors, developing innovative delivery systems, establishing biomarker-guided precision medicine strategies, and exploring non-enzymatic functions and downstream signaling networks of the IDO family. These efforts will help overcome the limitations of current therapies and provide new treatment paradigms for refractory diseases related to immune metabolic disorders.