USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24

Abstract

AbstractReprogramming of macrophages toward an M1 phenotype is a novel strategy to induce anticancer immunity. However, the regulatory mechanisms of M1 macrophage polarization and its functional roles in nasopharyngeal carcinoma (NPC) progression need to be further explored. Here we found that SPLUNC1 was highly expressed and responsible for M1 macrophage polarization. JAK/STATs pathway activation was involved in SPLUNC1-mediated M1 macrophage polarization. Importantly, regulation of SPLUNC1 in macrophages affected CM-mediated influence on NPC cell proliferation and migration. Mechanistically, USP7 deubiquitinated and stabilized TRIM24, which promoted SPLUNC1 expression via recruitment of STAT3 in M1 macrophages. Depletion of TRIM24 inhibited M1 macrophage polarization, which facilitated NPC cell growth and migration. However, over-expression of USP7 exhibited the opposite results and counteracted the tumorigenic effect of TRIM24 silencing. Finally, the growth and metastasis of NPC cells in vivo were repressed by USP7-induced M1 macrophage polarization via modulating TRIM24/SPLUNC1 axis. USP7 delayed NPC progression via promoting macrophage polarization toward M1 through regulating TRIM24/SPLUNC1 pathway, providing evidence for the development of effective antitumor immunotherapies for NPC.