In contrast, the TLR9 agonist vidutolimod combined with PD-1 blockade demonstrated preliminary efficacy in PD-1 inhibitor-resistant melanoma patients with immunologically cold TMEs, achieving an ORR of 25% (11/44; including 7 partial responses and 4 complete responses) (25), providing critical context for patient stratification strategies. The gene discussed is TLR9; the disease is melanoma.