The presence of high lactate, succinate, and other pro-tumor metabolites in the TME further supports the M1-to-M2 polarization through mechanisms such as the yes-1 associated protein (YAP) and NF-kB inhibition via the G protein-coupled receptor 81 (GPR-81)-mediated pathway (76, 77). Here, NFKB1 is linked to neoplasm.