Tumor-associated macrophages in non-small-cell lung cancer: From treatment resistance mechanisms to therapeutic targets

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide. Different treatment approaches are typically employed based on the stage of NSCLC. Common clinical treatment methods include surgical resection, drug therapy, and radiation therapy. However, with the introduction and utilization of immune checkpoint inhibitors, cancer treatment has entered a new era, completely revolutionizing the treatment landscape for various cancers and significantly improving overall patient survival. Concurrently, treatment resistance often poses a critical challenge, with many patients experiencing disease progression following an initial response due to treatment resistance. Increasing evidence suggests that the tumor microenvironment (TME) plays a pivotal role in treatment resistance. Tumor-associated macrophages (TAMs) within the TME can promote treatment resistance in NSCLC by secreting various cytokines activating signaling pathways, and interacting with other immune cells. Therefore, this article will focus on elucidating the key mechanisms of TAMs in treatment resistance and analyze how targeting TAMs can reduce the levels of treatment resistance in NSCLC, providing a comprehensive understanding of the principles and approaches to overcome treatment resistance in NSCLC. [Display omitted] •This review provides a comprehensive analysis of the mechanisms by which tumor-associated macrophages contribute to treatment resistance in non-small cell lung cancer.•The tumor microenvironment plays a pivotal role in treatment resistance, with tumor-associated macrophages being key contributors.•Immune checkpoint inhibitors have revolutionized the treatment landscape for non-small cell lung cancer and improved overall patient survival.•Strategies to target TAMs are discussed, offering potential approaches to reduce treatment resistance levels in non-small cell lung cancer.