Senescent Macrophages and the Lung Cancer Microenvironment: A New Perspective on Tumor Immune Evasion
Lexin Qin, Tingting Liang, Xinyu Zhu, Wentao Hu, Bo Li, Meidan Wei, Jiaxin Zhang, Jianxiang Li, Jinfeng Wang
Abstract
Lung cancer treatment is evolving, and the role of senescent macrophages in tumor immune evasion has become a key focus. This study explores how senescent macrophages interact with lung cancer cells, contributing to tumor progression and immune dysfunction. As aging impairs macrophage functions, including phagocytosis and metabolic signaling, it promotes chronic inflammation and cancer development. p16<sup>INK4a</sup>-positive macrophages are common in aged mice, and their clearance slows tumor growth, suggesting these cells support tumor proliferation and immune evasion. Targeting the senescence-associated secretory phenotype (SASP) and reprogramming senescent macrophages offers potential therapeutic benefits, including reversing immune aging and boosting anti-tumor immunity. However, translating these findings into clinical practice requires further molecular understanding and rigorous clinical trials.