Data from Intratumoral TREX1 Induction Promotes Immune Evasion by Limiting Type I IFN

• DOI: 10.1158/2326-6066.c.7267943
• Publication Date: 2024-06-04T07:59:52Z
• Authors: Eléonore Toufektchan; Alexandra Dananberg; Josefine Striepen; James H. Hickling; Abraham Shim; Yanyang Chen; Ashley Nichols; Mercedes A. Duran...; Lisa Mohr; Samuel F. Bakhoum; John Maciejowski
• Keywords: Evasion (ethics); Limiting

<div>Abstract<p>Chromosomal instability is a hallmark of human cancer that associated with aggressive disease characteristics. Chromosome mis-segregations help fuel natural selection, but they risk provoking cGAS-STING immune response through the accumulation cytosolic DNA. The mechanisms how tumors benefit from chromosomal while mitigating risks, such as enhanced surveillance, are poorly understood. Here, we identify cGAS-STING–dependent upregulation nuclease TREX1 an adaptive, negative feedback mechanism promotes evasion digestion loss diminishes tumor growth, prolongs survival host animals, increases infiltration, and potentiates to checkpoint blockade selectively in capable mounting type I IFN downstream STING. Together, these data demonstrate induction shields chromosomally unstable surveillance by dampening production suggest inhibitors might be used target have retained inherent ability mount STING.</p><p><i><a href="https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-23-1078" target="_blank">See related article Lim et al., p. 663</a></i></p></div>