Tumor‐Associated Macrophages: Key Players in the Non‐Small Cell Lung Cancer Tumor Microenvironment

ABSTRACT Background Lung cancer is among the most common and deadliest malignant tumors worldwide. It is often detected at late stages, resulting in unfavorable outcomes, with tumor cell heterogeneity and medication resistance. Tumor‐associated macrophages are among the key cells contributing to cancer progression. They are categorized into two primary phenotypes: Proinflammatory (M1) and anti‐inflammatory (M2) which are involved in the onset and progression of NSCLC. The role of common cytokines secreted by macrophages in the progression of lung cancer are described, and the effects of various substances such as RNA or protein on the differentiation and polarization of two phenotypes of macrophages are highlighted to characterize the impact of the immune state of tumors on therapeutic effect of treatments and patient prognosis. Researchers have primarily aimed to investigate innovative carriers and strategies based on macrophages to modify the tumor microenvironment. Objectives These approaches are often integrated with other treatments, particularly immunotherapy, to enhance therapeutic efficacy. Methods A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords “TAMs”, “NSCLC”, “Drug resistance”, and “therapy”. The available studies were screened for selection based on quality and relevance. Conclusions TAMs promote tumor invasion, growth, and metastasis by promoting angiogenesis and EMT. In addition, they contribute to the development of drug resistance and the immunosuppressive microenvironment establishment. The immunosuppressive factors secreted by TAM can weaken the activity of immune cells, inhibit their killing effect on tumors, leading to immune suppression and hindering the effectiveness of treatment. Therefore, TAM is a key target for the development of cancer immunotherapy. Various strategies are being explored, including reducing the recruitment of TAMs and influencing their polarization to treat NSCLC. In addition, TAMs based treatment systems can achieve precise delivery of drugs or gene interfering molecules without causing side effects.