Cancer-cell-derived cGAMP limits the activity of tumor-associated CD8+ T cells

This is the authors' abstract. We don't add key points for this paper.

Using a mouse tumor model with inducible cancer-cell-intrinsic cyclic GMP-AMP (cGAMP) synthase (cGAS) expression, we show that cancer-cell-derived cGAMP is essential and sufficient to trigger a sustained type I interferon response within the tumor microenvironment. This leads to improved CD8 + T cell-dependent tumor restriction. However, cGAMP limits the proliferation, survival, and function of stimulator of IFN genes (STING)-expressing, but not of STING-deficient, CD8 + T cells. In vivo , STING deficiency in CD8 + T cells enhances tumor restriction. Consequently, cancer-cell-derived cGAMP both drives and limits the anti-tumor potential of CD8 + T cells. Mechanistically, T cell-intrinsic STING is associated with pro-apoptotic and antiproliferative gene signatures. Our findings suggest that STING signaling acts as a checkpoint in CD8 + T cells that balances tumor immunity.