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Updated: Jan 13, 2026

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV
Published on: September 14, 2010
Single-cell and spatial transcriptomics reveal mTOR-driven cellular fate of spindle cells and immune evasion in
Ting Su1, Yongkai Yu1, Xuechen Cao1
1Department of Dermatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Background:
Classic Kaposi's sarcoma (CKS) is an angiogenic tumor with no standardized treatment. Increased mTOR pathway activity in tumors fuels oncogenesis by stimulating anabolic metabolism, cell proliferation, and angiogenesis. This study aimed to assess the therapeutic potential of mTOR inhibitor metformin in CKS patients.
Methods:
Two consecutive patients with biopsy-proven, CKS received metformin as monotherapy, and we further leverage single-cell RNA sequencing and spatial transcriptomics to uncover its underlying molecular mechanisms.
Results:
Rapid clinical response with no adverse effects was observed in 2 CKS patients. Further investigation identified characteristic spindle cells (SCs) exhibiting heightened activity in VEGF, mTOR, and hypoxia signaling pathways, suggestive of a terminal stromal differentiation state. Besides, the immune landscape was characterized by a high proportion of CD8+ Tex and NK cells displaying suppressed cytotoxicity and migration functions. Crucially, SCs were found to interact with immune cells predominantly via the CXCL9-CXCR3 signaling axis.
Conclusion:
This study reveals the mTOR-driven differentiation of SCs in KS pathogenesis aligning with rapid clinical improvement in CKS patients, which provides compelling evidence for metformin's therapeutic potential in CKS.
Insights
Metformin shows promise for treating Classic Kaposi's sarcoma (CKS). This mTOR inhibitor led to rapid clinical improvement in two patients by targeting spindle cells and influencing the tumor microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Classic Kaposi's sarcoma (CKS) is an angiogenic tumor lacking standardized treatment.
- Increased mechanistic target of rapamycin (mTOR) pathway activity drives CKS oncogenesis.
- The study explored metformin, an mTOR inhibitor, for CKS therapy.
Purpose of the Study:
- To assess the therapeutic potential of metformin in Classic Kaposi's sarcoma.
- To investigate the molecular mechanisms of metformin's action in CKS.
Main Methods:
- Two CKS patients received metformin monotherapy.
- Single-cell RNA sequencing and spatial transcriptomics were employed.
- Molecular mechanisms of metformin's efficacy were analyzed.
Main Results:
- Metformin induced rapid clinical responses with no adverse effects in CKS patients.
- Spindle cells showed heightened activity in VEGF, mTOR, and hypoxia pathways.
- Immune cells exhibited suppressed cytotoxicity and migration, with SC-immune cell interaction via CXCL9-CXCR3 axis.
Conclusions:
- Metformin demonstrates therapeutic potential for CKS.
- mTOR-driven differentiation of spindle cells is implicated in CKS pathogenesis.
- Metformin's efficacy aligns with observed clinical improvements in CKS patients.
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