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Updated: Dec 6, 2025

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

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Tumor-Derived cGAMP Regulates Activation of the Vasculature

Marco Campisi1,2, Shriram K Sundararaman2,3, Sarah E Shelton2,4

  • 1Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.

Frontiers in Immunology
|October 5, 2020
PubMed

Insights

Cancer cells lacking STING can still prime tumor vasculature for immune cell infiltration. Extracellular cGAMP from cancer cells activates endothelial STING, enhancing immune cell adhesion and tumor vascular permeability, crucial for anti-tumor immunity.

Area of Science:

  • Immunology
  • Cancer Biology
  • Vascular Biology

Background:

  • Intratumoral immune cell recruitment is vital for anti-tumor immunity, relying on cytosolic dsDNA sensing via the cGAS/STING pathway.
  • KRAS-LKB1 (KL) mutant lung cancer resists PD-1 blockade due to STING silencing, reduced chemoattractant production, and T cell exclusion.
  • Tumor vasculature critically regulates immune cell infiltration.

Purpose of the Study:

  • To investigate KL tumor-vascular interactions using a novel microfluidic model.
  • To elucidate the role of cancer cell-derived cGAS-STING signaling in priming tumor vasculature for immune cell infiltration.

Main Methods:

  • Development of a microfluidic model to study interactions between KL lung cancer cells and the tumor vasculature.
  • Analysis of dsDNA priming effects on LKB1-reconstituted tumor cells and microvasculature, including STING-deleted conditions.
  • Assessment of extracellular 2'3' cGAMP export, endothelial STING activation, and associated vascular changes (permeability, adhesion molecule expression).

Main Results:

  • dsDNA priming of LKB1-reconstituted tumor cells activates the microvasculature, irrespective of tumor cell STING deletion.
  • Cancer cell cGAS-driven export of 2'3' cGAMP activates STING signaling in endothelial cells.
  • This activation, along with type 1 interferon, increases vascular permeability and expression of E selectin, VCAM-1, and ICAM-1, promoting T cell adhesion.

Conclusions:

  • Tumor cell cGAS-STING signaling has a dual role: producing T cell chemoattractants and priming the tumor vasculature.
  • Extracellular cGAMP released by cancer cells can activate endothelial STING, facilitating immune cell infiltration.
  • This pathway represents a potential therapeutic target for enhancing anti-tumor immunity in STING-deficient lung cancers.
Keywords:
2′3′-cGAMPKRASLKB1STINGT cellendothelial cellsmicrofluidic culture

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