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.

Abstract

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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