Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: A critical and challenging process in immunotherapy is to identify cancer patients who could benefit from immune checkpoint inhibitors (ICIs). Exploration of predictive biomarkers could help to maximize the clinical benefits. Eph receptors have been shown to play essential roles in tumor immunity. However, the association between EPH gene mutation and ICI response is lacking.
Methods: Clinical data and whole-exome sequencing (WES) data from published studies were collected and consolidated as a discovery cohort to analyze the association between EPH gene mutation and efficacy of ICI therapy. Another independent cohort from Memorial Sloan Kettering Cancer Center (MSKCC) was adopted to validate our findings. The Cancer Genome Atlas (TCGA) cohort was used to perform anti-tumor immunity and pathway enrichment analysis.
Results: Among fourteen EPH genes, EPHA7-mutant (EPHA7-MUT) was enriched in patients responding to ICI therapy (FDR adjusted P < 0.05). In the discovery cohort (n = 386), significant differences were detected between EPHA7-MUT and EPHA7-wildtype (EPHA7-WT) patients regarding objective response rate (ORR, 52.6% vs 29.1%, FDR adjusted P = 0.0357) and durable clinical benefit (DCB, 70.3% vs 42.7%, FDR adjusted P = 0.0200). In the validation cohort (n = 1144), significant overall survival advantage was observed in EPHA7-MUT patients (HR = 0.62 [95% confidence interval, 0.39 to 0.97], multivariable adjusted P = 0.0367), which was independent of tumor mutational burden (TMB) and copy number alteration (CNA). Notably, EPHA7-MUT patients without ICI therapy had significantly worse overall survival in TCGA cohort (HR = 1.33 [95% confidence interval, 1.06 to 1.67], multivariable adjusted P = 0.0139). Further gene set enrichment analysis revealed enhanced anti-tumor immunity in EPHA7-MUT tumor.
Conclusions: EPHA7-MUT successfully predicted better clinical outcomes in ICI-treated patients across multiple cancer types, indicating that EPHA7-MUT could serve as a potential predictive biomarker for immune checkpoint inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852135 | PMC |
| http://dx.doi.org/10.1186/s12916-020-01899-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New strategies to enhance the efficacy of PD-1/PD-L1 inhibitors in treating microsatellite stable colorectal cancer.
Future Oncol
September 2025
Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China.
Immune checkpoint therapy has demonstrated significant potential in the treatment of various solid tumors. Among these, tumor-induced immunosuppression mediated by programmed cell death protein 1 (PD-1) represents a critical checkpoint. PD-1/programmed death-ligand 1 (PD-L1) inhibitors have been proven to exhibit substantial efficacy in solid tumors such as melanoma and bladder cancer.
View Article and Find Full Text PDFTOX-induced lnc-SUMF2-8 compromises antitumor function and anti-PD-1 response of CD8 T cells via lysosome-dependent degradation of TCF-1.
Mol Ther
September 2025
Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:
The reduction of TCF-1 during CD8 T cell exhaustion leads to attenuated antitumor activity and diminished responsiveness to immune checkpoint inhibitors. However, how TCF-1 is downregulated remains unclear. Here, we showed that during CD8 T cell exhaustion, lnc-SUMF2-8, induced by transcription factor TOX, can bind to cytosolic TCF-1, and direct it to the lysosome for degradation.
View Article and Find Full Text PDFParasitic infections of the central nervous system (CNS) represent a considerable health burden in low- and middle-income countries. During chronic disease, parasites modulate host immunity to ensure long-term persistence while limiting collateral tissue damage. A key feature of this immune remodeling is the progressive T-cell dysfunction that may culminate in T-cell exhaustion, characterized by increased expression of inhibitory receptors (TIM-3, LAG-3, KLRG1), checkpoint molecules (PD-1, PD-L1), suppressor of cytokine signaling-1 (SOCS1), and arginase-1.
View Article and Find Full Text PDFASO Practice Guidelines Series: Soft Tissue Sarcoma of the Extremities and Superficial Trunk.
Ann Surg Oncol
September 2025
Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Soft tissue sarcomas (STS) are a heterogeneous group of rare malignant tumors arising from mesenchymal tissues, with extremity and superficial trunk STS (eSTS) comprising the majority of cases. The management of localized eSTS requires a multidisciplinary approach to optimize oncologic and functional outcomes. This review outlines the natural history, diagnostic workup, and treatment principles for localized eSTS, emphasizing the role of histology-specific considerations in guiding management strategies.
View Article and Find Full Text PDFClinical utility of comprehensive genomic profiling test for colorectal cancer: a single institution prospective observational study.
J Cancer Res Clin Oncol
September 2025
Division of Gastroenterology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
Purpose: Next-generation sequencing (NGS) has revolutionized cancer treatment by enabling comprehensive cancer genomic profiling (CGP) to guide genotype-directed therapies. While several prospective trials have demonstrated varying outcomes with CGP in patients with advanced solid tumors, its clinical utility in colorectal cancer (CRC) remains to be evaluated.
Methods: We conducted a prospective observational study of CGP in our hospital between September 2019 and March 2024.