Unraveling tumor associated macrophage biology in gynecological cancers for targeted therapy in the single cell omics era.

The tumor microenvironment (TME) has long been the subject of cancer research, particularly in deciphering the complicated mechanisms underlying tumor development. Tumor associated macrophages (TAMs), as key components of the TME, exhibit remarkable heterogeneity and drive complex interactions that influence immune evasion and therapeutic resistance. Recent technological advancements, particularly single-cell RNA sequencing, have enabled the precise dissection of TAM subpopulations, offering unprecedented insights into their functional diversity. Gynecological cancers represent a global health burden with high morbidity and mortality. Despite advances in chemotherapy and immunotherapy, treatment efficacy remains suboptimal in advanced-stage patients, underscoring the urgent need to explore cellular mechanisms underlying therapeutic failure. This review aims to summarize emerging evidence on TAM subclusters in gynecological malignancies, highlight the context-dependent phenotypic plasticity of TAMs, point out the phenotype-specific roles in tumor progression and drug resistance and evaluate translational strategies targeting specific subtypes to improve clinical outcomes.