CD47 Blockade Inhibits Tumor Progression through Promoting Phagocytosis of Tumor Cells by M2 Polarized Macrophages in Endometrial Cancer.

ABSTRACT: There are rapidly emerging efforts to explore tumor-associated macrophages (TAMs) as a tumor therapy target. Tumor cells express CD47, which can interact with the macrophages' SIRP? transmitting a "don't eat me" signal to macrophages. The expression of CD47 increases in various tumors to evade immune attack. However, the expression of CD47 in endometrial cancer (EC) and the role of CD47-SIRP? in the TAMs which mediate the progression of EC remain unclear. Our study shows that there are increased TAMs in EC which dominantly consist of M2 macrophages and contribute to the progression of EC. We confirm that CD47 is highly expressed in EC tissue using the TCGA database, qPCR, and flow cytometry. Instead of directly promoting the apoptosis of EC cells, anti-CD47 blocking antibody promoted phagocytosis of EC cells by macrophages and the increased phagocytosis ability was mediated by M2 macrophages in a coculture assay. Besides, CD47 blockade inhibited the growth of the EC tumors in vivo and increased the infiltration of macrophages with antitumor ability in the tumor microenvironment (TME). These findings might assist in developing promising strategies that blocked the CD47-SIRPa interaction for EC therapy.

SUBMITTER: Gu S 

PROVIDER: S-EPMC6247569 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature