Tumor-Associated Macrophages in Lung Cancer: Origins, Functional Heterogeneity, and Therapeutic Implications

Yeqing Tao,1,* Jian Xiao,2,* Yafang Li,1 Aiping Zou3 1Endoscopy Center, The First People’s Hospital of Jiashan, Jiaxing, 314100, People’s Republic of China; 2Department of Orthopedics, The First People’s Hospital of Jiashan, Jiaxing, 314100, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jiashan, Jiaxing, 314100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aiping Zou, Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jiashan, Jiaxing, 314100, People’s Republic of China, Email [email protected]: Tumor-associated macrophages (TAMs) are a heterogeneous population of immune cells that play a pivotal role in the tumor microenvironment (TME) of lung cancer. TAMs, which include both monocyte-derived macrophages (MDMs) and tissue-resident macrophages (TRMs), exhibit distinct functions that influence tumor progression, metastasis, and response to therapy. Recent studies have highlighted the spatiotemporal heterogeneity of TAMs, with MDMs primarily promoting tumor growth and immune suppression, while TRMs contribute to tissue homeostasis but can be reprogrammed to support tumor progression. Both subtypes contribute to the formation of an immunosuppressive TME, facilitate tumor metastasis through matrix remodeling, and contribute to therapeutic resistance by modulating the efficacy of chemotherapy, radiation therapy, and immunotherapy. Understanding the specific roles and heterogeneity of MDMs and TRMs as components of TAMs in lung cancer opens avenues for targeted therapies, such as inhibiting their recruitment, reprogramming their polarization, or blocking their pro-tumorigenic functions. This review synthesizes current knowledge on TAMs in lung cancer, highlighting their dual roles and the potential for developing novel therapeutic strategies that target these macrophages to improve patient outcomes.Keywords: tumor microenvironment, macrophage polarization, immunotherapy, therapeutic resistance