The upregulation of WFDC2 during ICI therapy may reflect the activation of resistance pathways independent of the PD-1/PD-L1 axis or may signal tumor adaptation processes, such as epithelial–mesenchymal transition, increased tumor burden, or stromal remodeling, all of which have been associated with immunotherapy resistance [35,36]. The gene discussed is WFDC2; the disease is neoplasm.