The Unfolded Protein Response in Immunogenic Cell Death and Cancer Immunotherapy

The unfolded protein response(UPR) is a conserved pathway that is stimulated when endoplasmic reticulum (ER) proteostasisis disturbed or lost. Accumulating evidence indicates that chronic activation of the UPR supports the main hallmarksof cancerby favoring cancer cell-autonomous and nonautonomous processes, which ultimately foster the immunosuppressive and protumorigenic microenvironment. However, certain forms of therapy-induced ER stress can elicit immunogenic cancer cell death (ICD), which enables the release of key immunostimulatory or danger signals, eventually driving efficient antitumor immunity. In this review, after a brief discussion of the interplay between ER stress and protumorigenic inflammation, we review the relevance of therapy-mediated ER stress pathways in evoking ICD and how they could be used to optimize current immunotherapy approaches against cancer.