• Of the 64 PitNET tissues, invasive PitNETs were related to high infiltration of M2-like tumor-associated macrophages (TAMs). • Lactate secreted from PitNET cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PitNET invasion via the CCL17/CCR4/mTORC1 axis. This evidence concerns the gene CCR4 and neoplasm.