Mutations such as CALR del52 and CALR ins5 in myeloproliferative neoplasms, as well as truncations like CALR E405* in solid tumors, that disrupt the C-terminal Lys-Asp-Glu-Leu (KDEL) ER-retention motif, leading to aberrant secretion via Golgi-mediated exocytosis can act as local immunological decoys, saturating receptors like CD91 on antigen-presenting cells.7 As a result, such mutant forms of CALR can impair DC phagocytosis, suppressing CD8+ T cell responses, thus undermining the efficacy of chemotherapy and immune checkpoint inhibitors (ICI). This evidence concerns the gene CALR and myeloproliferative disorder.