We demonstrated that CTCF‐transcribed LncRNA PACERR directly interacts with CTCF, and the CTCF/PACERR complex recruits the acetyltransferase EP300 to increase the chromatic accessibility of PTGS2 locus, resulting in upregulated PTGS2 expression, thereby promoting the M2 polarization and pro‐tumour functions of TAMs. Here, EP300 is linked to neoplasm.