SMAD2 and cancer: Platelets increase the expression of PD-L1 in cancer cells mainly through a number of signaling pathways: Platelets and platelet secretion products can activate NF-κB, TGF-β/Smad and JAK/STAT pathways in tumor cells (49), which also increase the expression of PD-L1 in cancer cells exposured to platelets directly through Smad2/3 and NF-κB signaling pathways, and increases PD-L1 mostly through the TGFβR1/Smad signaling pathway exposured to platelets indirectly (45).