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- W4249187454 abstract "The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single disseminated cancer cells (DCCs) lacking expression of cytokeratin 19 (CK19) and major histocompatibility complex class I (MHCI). We created a mouse model to determine how these DCCs develop. Intraportal injection of immunogenic PDA cells into preimmunized mice seeded livers only with single, nonreplicating DCCs that were CK19- and MHCI- The DCCs exhibited an endoplasmic reticulum (ER) stress response but paradoxically lacked both inositol-requiring enzyme 1α activation and expression of the spliced form of transcription factor XBP1 (XBP1s). Inducible expression of XBP1s in DCCs, in combination with T cell depletion, stimulated the outgrowth of macrometastatic lesions that expressed CK19 and MHCI. Thus, unresolved ER stress enables DCCs to escape immunity and establish latent metastases.Copyright © 2018, American Association for the Advancement of Science. PMID: 29773669 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: P30 CA045508 NCI NIH HHS, United States Grant ID: P30 CA008748" @default.
- W4249187454 created "2022-05-12" @default.
- W4249187454 creator A5028552905 @default.
- W4249187454 creator A5085915684 @default.
- W4249187454 date "2018-10-11" @default.
- W4249187454 modified "2023-09-27" @default.
- W4249187454 title "Faculty Opinions recommendation of Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases." @default.
- W4249187454 doi "https://doi.org/10.3410/f.733251079.793551628" @default.
- W4249187454 hasPublicationYear "2018" @default.
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