Here, we report that macrophage‐specific deletion of the SUMO‐specific protease Sentrin/SUMO‐specific protease 3 promotes macrophage polarization towards M2 in bone marrow‐derived macrophage (BMDM) induced by interleukin 4 (IL‐4)/IL‐13 and in an ex vivo model (murine Py8119 cell line), as well as in a mouse orthotopic tumor model. Here, IL4 is linked to neoplasm.