Synergistic Mechanisms of Combined Anti-Angiogenic Therapy and Immunotherapy in Non-small Cell Lung Cancer

In the tumor microenvironment, a bidirectional feedback regulation exists between aberrant angiogenesis and antitumor immunity, which provides a basis for the synergistic effects of antiangiogenic therapy and immunotherapy. The underlying mechanisms include relief of immunosuppression mediated by proangiogenic factors, induction of vascular normalization to reshape the immune microenvironment, and formation of a positive immune-vascular feedback loop. Based on these mechanisms, the combination of antiangiogenic therapy and immunotherapy has demonstrated synergistic efficacy in advanced non-small cell lung cancer (NSCLC) and is gradually being moved forward to the neoadjuvant setting. However, in the perioperative treatment of resectable lung cancer, this regimen still faces challenges, including primary resistance, a brief window of vascular normalization, and an unclear understanding of spatial interaction mechanisms. This review systematically elucidates the synergistic mechanisms of antiangiogenic agents combined with immunotherapy in NSCLC and the latest advances of this combination strategy in the neoadjuvant therapy setting, aiming to provide a reference for clinical practice.