Development and Status of Therapeutic Strategies Targeting MDSCs in Lung Cancer Immunotherapy

Abstract

Myeloid suppressor cells (MDSCs) exert immunosuppressive effects in the lung cancer microenvironment through various mechanisms, including metabolic regulation, cell surface molecular action, and secretion of immunosuppressive cytokines, which weaken the host's anti-tumor immune response and promote tumor growth and immune escape. This study focused on the role of key signaling pathways (such as JAK/STAT, PI3K/Akt/mTOR, NF-κB) and its related genes (ARG1, iNOS, PD-L1, S100A8/A9) in immunosuppression during the development and differentiation of MDSCs. In addition, the paper summarizes current therapeutic strategies targeting MDSCs, including ARG1 and iNOS inhibitors, PD-L1/PD-1 immune checkpoint inhibitors, and innovative therapies blocking the S100A8/A9 pathway, and explores the potential of multi-target combination therapy. However, the heterogeneity of MDSCs, poor treatment selectivity, side effects and treatment resistance remain major challenges. Further studies should concentrate on the design of multi-target combination therapy strategies, the targeting selectivity optimization, and reliable biomarkers to continue further increasing efficacy and safety in immunotherapy for lung cancer.