A subset of MDSCs that express murine Schlafen4 (SLFN4) or its human ortholog SLFN12L polarize in the Helicobacter-inflamed stomach coincident with intestinal or spasmolytic polypeptide-expressing metaplasia (SPEM). We propose that individuals with a more robust response to damage-activated molecular patterns (DAMPs) and increased Toll-like receptor (TLR9) expression are predisposed to the neoplastic complications of Helicobacter infection.