Related Experiment Video
Updated: Apr 22, 2026
09:45
Microfluidics-based High-throughput Circulating Tumor Cell Sorting and Single-cell Sequencing Technology
Published on: November 14, 2025
965
Single-Cell Sequencing Plus Spatial Transcriptomics: Dissecting Tumor Heterogeneity, Immunosuppression, and Potential
Yingjing Wang1, Xia Wu1, Xiao Cheng1
1Ningbo Clinical Pathology Diagnosis Center, Ningbo, China.
The American Journal of Pathology
|April 20, 2026
Summary
ASPSCR1::TFE3 renal cell carcinoma (RCC) exhibits high metastasis and immune suppression. Targeting MDK-LRP1 interactions and the C3 subtype may improve immunotherapy for this RCC variant.
Area of Science:
- Oncology
- Genitourinary Pathology
- Cancer Immunology
Background:
- ASPSCR1::TFE3 renal cell carcinoma (RCC) presents a unique subtype with aggressive characteristics, including frequent lymph node metastasis and poor prognosis.
- The underlying pathogenesis and immune microenvironment of ASPSCR1::TFE3 RCC remain poorly understood, limiting effective clinical interventions.
- Clear cell renal cell carcinoma (ccRCC) serves as a comparator for understanding the distinct features of ASPSCR1::TFE3 RCC.
Purpose of the Study:
- To elucidate the distinct molecular and immune profiles of ASPSCR1::TFE3 RCC compared to ccRCC.
- To identify key cellular subtypes and molecular pathways driving the aggressive phenotype of ASPSCR1::TFE3 RCC.
- To investigate the immune microenvironment and potential mechanisms of immune escape in ASPSCR1::TFE3 RCC.
Main Methods:
- Comparative analysis of formalin-fixed paraffin-embedded (FFPE) samples from ASPSCR1::TFE3 RCC and ccRCC.
- Application of single-cell sequencing to dissect cellular heterogeneity.
- Utilisation of high-resolution spatial transcriptomics to map the tumor microenvironment.
Main Results:
- Significant divergence in tumor and immune microenvironments between ASPSCR1::TFE3 RCC and ccRCC.
- ASPSCR1::TFE3 RCC is characterized by oxidative phosphorylation and epithelial-mesenchymal transition pathways, contrasting with interferon response and hypoxia in ccRCC.
- Tumor cells in ASPSCR1::TFE3 RCC segregate into C3/C4 subtypes, with the C3 subtype showing heightened expression of pro-invasive genes (MDK, MMP7, VCAN) linked to metastasis.
- An immunosuppressive phenotype in ASPSCR1::TFE3 RCC is marked by increased macrophages and exhausted T/NK cells.
- Tumor cell-macrophage interactions via MDK-LRP1 signaling contribute to immune escape.
Conclusions:
- ASPSCR1::TFE3 RCC is confirmed as a highly malignant tumor with potent immunosuppressive features and significant metastatic potential.
- The enrichment of the C3 subtype and elevated MDK expression are key molecular drivers of ASPSCR1::TFE3 RCC's aggressive behavior.
- Findings offer novel insights for targeted therapies and hold promise for expanding immunotherapy eligibility in ASPSCR1::TFE3 RCC patients.
