PDCD1 and neoplasm: For example, in pancreatic cancer, the dense fibrotic stroma and the presence of immunosuppressive cytokines such as TGF-β severely limit the effectiveness of PD-1 inhibitors.326,327 This highlights the need for combination therapies that modify the TME.328,329 These findings emphasize the critical need for combination therapies designed to modulate the tumor microenvironment.