Tumor-associated macrophages-derived exosomes: research advances in breast and gynecological cancers

Abstract Exosomes secreted by tumor-associated macrophages (TAMs) function as pivotal mediators of intercellular communication within tumor microenvironments (TME). These vesicles actively accelerate cancer progression through multiple pathways: driving tumor cell proliferation and metastasis, reprogramming tumor metabolism, inducing angiogenesis to support nutrient supply, facilitating immune evasion, enhancing resistance to therapies, and sustaining cancer stem cell populations. In breast and gynecological malignancies specifically, TAM-derived exosomes (TDEs) demonstrate broad functional impact across these critical processes. Beyond their pathological roles, these exosomes show promise as both diagnostic biomarkers and therapeutic targets. This review not only summarizes the functional roles of TDEs but also delves into the underlying molecular mechanisms governing their biogenesis, secretion, and uptake, including the ESCRT-dependent and -independent pathways, the regulatory roles of Rab GTPases (e.g., Rab27a) in exosome release, the selective packaging of oncogenic miRNAs mediated by RNA-binding proteins (e.g., hnRNPA2B1), and the modulation of these processes by hypoxic and metabolic cues within the TME. Furthermore, we outline promising future research directions aimed at translating this knowledge into improved prevention and treatment strategies for female-specific cancers.