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, 79 (15), 3815-3817

STING (Or SRC) Like an ICB: Priming the Immune Response in Pancreatic Cancer

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STING (Or SRC) Like an ICB: Priming the Immune Response in Pancreatic Cancer

Stanley I Gutiontov et al. Cancer Res.

Abstract

Pancreatic adenocarcinoma is associated with a poor prognosis and resistance to immune checkpoint blockade. Zhang and colleagues demonstrate that inhibiting DNA repair by pharmacologic blockade or siRNA silencing of ataxia telangiectasia mutated (ATM) increases type I IFN release via a cGAS/STING-independent, SRC-dependent mechanism in models of pancreatic cancer. Furthermore, combining ATM inhibition and radiotherapy amplifies type I IFN signaling, increases programmed death ligand 1 (PD-L1) expression, tumor CD8+ T cells, and proinflammatory tumor macrophages. Finally, the combination of ATM silencing, radiotherapy, and PD-L1 blockade markedly improves in vivo murine tumor responses, supporting further investigation of this promising approach in pancreatic adenocarcinoma.See related article by Zhang et al., p. 3940.

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