This occurs through the activation of Toll-like receptor 2 (TLR2) and NF-κB signaling, while lactate produced by cancer cells further feeds back on NF-κB to increase PD-L1 expression, ultimately reinforcing the immunosuppressive profile of macrophages.280 Stromal cells also play essential roles in the premetastatic TME. The gene discussed is TLR2; the disease is cancer.