Fig. 8. Model for PKM2 regulated TAM-induced PD-L1 expression and immunosuppression in PDAC.

In the proposed model, TGF-β1 secreted by TAMs induces the nuclear translocation of PKM2, resulting in PD-L1 overexpression in PDAC cells by the Jak-Stat1 pathway, which leads to NK cell inactivation and dysfunction. Instead, the inhibition of PKM2 or PD-L1 leads to enhanced antitumor immunity in PDAC models.