• Author
    Sin Yee Lim
  • Discovery PI

    Joseph G. Crompton, MD, PhD

  • Project Co-Author

    Hy Dao, Tyler McCaw, Kao Kawasumi, Adhitya Ram, Atul Thirumalai, Sandra Chane, Chen Yuan Kam

  • Abstract Title

    Peri-operative normalization of tumor vasculature to prevent surgical-induced tumor growth

  • Discovery AOC Petal or Dual Degree Program

    Basic, Clinical, & Translational Research

  • Abstract

    Introduction

    Surgery remains the oldest and most effective treatment for solid cancers. When a tumor is not completely removed, the impact of surgery on the tumor microenvironment (TME) is poorly understood. Prior studies show that (i) surgery stimulates VEGF-mediated angiogenesis and (ii) VEGF promotes endothelial cell anergy—a state where endothelial cells fail to express adhesion molecules required for leukocyte transmigration. We therefore hypothesized that surgical intervention induces endothelial cell anergy, reducing CD8+ T cell trafficking in the TME and accelerating residual tumor growth.

    Methods

    We developed a novel model of incomplete tumor resection using a p53/Kras-driven sarcoma mouse model (TAO1). On day 10, mice underwent no surgery (NS) or 50% tumor resection (R2). In vivo two-photon excitation microscopy (TPEF) was performed at POD3 to evaluate vascular remodeling. Flow cytometry quantified VEGF-driven changes in immune and stromal populations. Therapeutic targeting of angiogenesis was assessed using VEGF-A blockade.

    Results

    TPEF revealed abnormal, tortuous blood vessels with turbulent flow in residual tumor after incomplete resection. Flow cytometry showed reduced CD8+ T cells infiltration after incomplete surgery, correlating with accelerated tumor growth. Perioperative anti-VEGF-A treatment restored CD8 T cell infiltration and suppressed tumor progression.

    Conclusions

    Incomplete tumor resection promotes a pro-tumorigenic microenvironment characterized by aberrant angiogenesis and endothelial cell anergy, impairing anti-tumor immunity. Peri-operative anti-VEGF therapy can normalize vasculature to enhance immune cell infiltration and mitigate tumor progression.

     

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