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Cancer Res. 2019 Aug 1;79(15):3815-3817. doi: 10.1158/0008-5472.CAN-19-1700.

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

Author information

1
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
2
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois. rrw@radonc.uchicago.edu.

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.

PMID:
31371279
DOI:
10.1158/0008-5472.CAN-19-1700
[Indexed for MEDLINE]

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