Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases

Abstract

Chronic stress as a survival tactic Most patients with pancreatic ductal adenocarcinoma (PDA) develop liver metastases after surgical removal of their primary tumor. These metastases are thought to potentially arise from quiescent disseminated cancer cells, likely present at the time of surgery, which evade elimination by the immune system. Pommier et al. explored how these quiescent cells survive by analyzing mouse models and tissue samples from patients with PDA. They found that disseminated cancer cells do not express a cell surface molecule that triggers killing by T cells. This phenotypic feature is linked to their inability to resolve endoplasmic reticulum stress. When this stress is resolved, the disseminated cells begin proliferating and form metastases. Science , this issue p. eaao4908