Immune heterogeneity and therapeutic resistance in gynecological malignancies.

Gynecological malignancies are characterized by profound cellular heterogeneity, dynamic immune remodeling, and frequent therapeutic resistance, which together limit durable clinical responses. Single-cell sequencing has emerged as a powerful approach for dissecting tumor ecosystems at unprecedented resolution, enabling the identification of malignant subclones, immune cell states, stromal subsets, lineage trajectories, and intercellular communication networks. In cervical cancer, single-cell studies have revealed epithelial diversity, HPV-associated immune suppression, exhausted T/NK-cell populations, macrophage polarization, and genomic alterations linked to chemoradiotherapy resistance. In ovarian cancer, single-cell analyses have refined the understanding of fallopian tube origin, molecular subtypes, metastatic dissemination, ascites-associated immune suppression, platinum resistance, and tertiary lymphoid structure-related immune phenotypes. In endometrial cancer, single-cell profiling has uncovered heterogeneous cancer-associated fibroblast populations, epithelial biomarkers, and stromal-immune interactions with prognostic relevance. This review summarizes recent advances in single-cell sequencing across cervical, ovarian, and endometrial cancers, with particular emphasis on immune heterogeneity, tumor-microenvironment crosstalk, therapeutic resistance, and emerging opportunities for precision immunotherapy.