TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy

Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) play a central role in tumor progression and therapeutic resistance in gynecological malignancies, including ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC). This review systematically summarizes common regulatory mechanisms and tumor-specific variations in TAMs across these three malignancies, emphasizing the dual-origin developmental trajectories of tissue-resident macrophages and monocyte-derived macrophages, the CCL2-CCR2 and CSF1-CSF1R core signaling axes, and the regulation of TAMs’ functional polarization by hypoxia and metabolic reprogramming. Furthermore, the molecular mechanisms through which TAMs mediate immunosuppression and therapeutic resistance via physical barrier construction, metabolic competition, and antigen presentation impairment are analyzed, and the specific characteristics of the peritoneal microenvironment in OC, HPV-driven mechanisms in CC, and hormonal regulation in EC are compared. Therapeutic strategies targeting TAM recruitment, survival, and phenotypic reprogramming are discussed, along with TAM markers, and may provide a theoretical foundation and clinical indications for overcoming immune therapeutic resistance in gynecological malignancies.