Macrophage polarization in gynecologic malignancies: key signaling pathways and clinical perspectives

Gynecological malignancies represent a significant global health burden for women worldwide. Tumor-associated macrophages (TAMs), as a critical component of the immune system, play a pivotal role within the tumor microenvironment (TME). Modulating signaling pathways in the TME can promote the polarization of TAMs toward the M1 phenotype, thereby enhancing anti-tumor effects and suppressing tumor growth and metastasis. The rapid advancement of nano-drug delivery systems (NDDSs) has expanded the potential for clinical translation of immunotherapies targeting TAMs. Our review provides an overview of the latest research progress on TAMs polarization-related signaling pathways and the use of NDDSs for targeted TAMs therapy in gynecological malignancies. Concurrently, the challenges encountered during the clinical translation of these therapeutic measures and future directions are discussed, aiming to provide novel insights for the immunotherapy of gynecological malignancies.