Sequential anlotinib (anti-angiogenic drug) and camrelizumab (PD-1 inhibitor) combination therapy overcame three biological barriers: (1) angiogenesis inhibition reversed PD-L1 primary resistance by remodeling the tumor microenvironment; (2) treatment induced neoantigens bypassed TMB-L/MSS limitations; (3) multi-target synergy against seven driver mutations. The gene discussed is CD274; the disease is neoplasm.