MANF and hepatocellular carcinoma: Moreover, one study has revealed that MANF supplementation in monocyte-derived macrophages (MDMs) enhances the interaction between heat shock factor 1 (HSF1) and heat shock protein 70 (HSP-70), thereby inhibiting the nuclear import of HSF1, which in turn negatively regulates the expression of HSP70-1 in macrophages, reprograms tumor-associated macrophages (TAMs) into an M1-like phenotype, and ultimately suppresses HCC neovascularization to achieve therapeutic efficacy [98].