Immunogenic cell death (ICD) is a key factor for generating antitumor immunity. Endoplasmic reticulum (ER) stress triggers the release of damage-associated molecular patterns (DAMPs), thus inducing immunogenicity. We developed a polypeptide-based K+ ionophore that perturbed ion homeostasis and elicited a prolonged ER stress. The ER stress not only fosters an oxidative environment that activates mitochondria-dependent apoptosis pathways but also drives immune responses by releasing DAMPs. The ionophore suppressed tumor proliferation in vitro and in vivo based on the pro-apoptotic activity and immunogenicity.
Keywords: DAMP release; ER stress; dendritic cell maturation; immunogenic cell death; potassium ion efflux.