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The cGAS-STING pathway in the tumor immune microenvironment: Multidimensional regulation and therapeutic implications

Siyu Wu1, Boyan Tian1, Yahui Sun1

  • 1Heilongjiang University of Chinese Medicine, , Harbin, China.

Critical Reviews in Oncology/Hematology
|May 15, 2026
PubMed

Insights

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates the tumor immune microenvironment (TIME). Targeting this pathway offers new strategies for cancer immunotherapy by reprogramming the TIME.

Area of Science:

  • Immunology
  • Cancer Biology
  • Systems Biology

Background:

  • The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is crucial in cancer immunotherapy.
  • Current understanding often focuses on linear signaling or cell-autonomous functions, neglecting the tumor immune microenvironment's (TIME) complexity.
  • A comprehensive framework is needed to understand crosstalk among tumor, immune, and stromal cells within the TIME.

Purpose of the Study:

  • To explore the cGAS-STING pathway's role beyond cell-intrinsic functions.
  • To adopt a systems-level perspective on cGAS-STING signaling within the dynamic TIME.
  • To propose novel therapeutic strategies for cancer immunotherapy.

Main Methods:

  • Systems-level analysis of cGAS-STING signaling.
  • Investigation of spatiotemporal context and dynamic regulation.
  • Delineation of non-cell-autonomous effects within the multicellular TIME network.

Main Results:

  • cGAS-STING activity exerts context-dependent, non-cell-autonomous effects across the TIME.
  • The pathway acts as a regulatory axis orchestrating immune-ecological reconfiguration of the microenvironment.
  • It functions beyond a generic immune amplifier, influencing the TIME's overall ecology.

Conclusions:

  • Next-generation cancer immunotherapies require moving beyond indiscriminate pathway activation.
  • Precision-targeted intervention and microenvironmental reprogramming are key for durable responses.
  • A systems-level understanding facilitates the rational design of advanced cancer immunotherapies.
Keywords:
CGAS-STING pathwayImmune cellsImmunotherapyStromal cellsTumor immune microenvironment

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