Fig. 8: Illustrative working model of SET-mediated macrophage positioning in hypoxic tumor areas.

Various chemotactic signals derived from hypoxic tumor regions induced nuclear export of SET by activating PKC-CK2α in macrophages. Cytoplasmic SET accumulation further enhances ERK and P38 signaling by inhibiting PP2A, ultimately driving macrophages to the hypoxic region (a). The loss of SET causes TAMs to be retained in the area with blood vessels and away from hypoxic areas, thereby regaining the antitumor phenotype (b).