biostudies-otherUnknownShakti P PattanayakHomo sapiens (human)Mus musculus (mouse)https://www.ebi.ac.uk/biostudies/studies/S-BSST2345biostudies-otherhttpsWilliam C MerrickBelinda WillardTimothy A. ChanBoaz TiroshHong WangZheng-Rong LuShakti P PattanayakfalseInhibition of KDEL receptors remodels the tumor microenvironment for robust T cell independent tumor regressionTumor immunotherapy is supported by low-grade inflammatory conditions at the microenvironment, triggered by immunogenic cell death (ICD). However, ICD is dampened when tumors acquire resistance, affecting immune recognition. KDEL receptors (KDELRs), through a retrograde Golgi-to-ER transport, prevent spontaneous secretion of KDEL proteins. We report that inhibition of a single KDELR in a minor fraction of tumor cells, primarily KDELR2, provokes robust infiltration of macrophages and neutrophils into the tumor microenvironment, resulting in a complete regression of both immunogenic and non-immunogenic tumors independently of T cells. Importantly, in the course of regression, anti-tumor T cells are primed, conferring protection against a second challenge. Recapitulated by intratumoral delive2025-12-24T00:00:00Z2026-05-27T12:34:44.016Z2025-12-23T19:37:04.18ZS-BSST2345https