HRG (histidine-rich glycoprotein) levels are decreased in the TME, and researchers have increased tumor levels by using a genetic gain-of-function strategy to find that HRG derived from these tumor cells inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through the downregulation of PIGF (placental growth factor), suggesting that HRG contributes to the skewing of TAMs to an antitumor polarization phenotype 70. Here, PIGF is linked to neoplasm.