Beyond Tumor-Intrinsic STAT3: Integrating Metabolic and Immune Communication in the Tumor Microenvironment of Cervical, Ovarian, and Endometrial Cancers

Abstract

Simple Summary Cervical, ovarian, and endometrial cancers are biologically heterogeneous diseases in which tumor progression is shaped not only by malignant cells but also by the surrounding tumor microenvironment. This complex environment is composed of immune cells, stromal cells, blood vessels, and metabolic factors that continuously communicate with tumor cells, promoting immune suppression, therapy resistance, and disease progression. Increasing evidence identifies Signal Transducer and Activator of Transcription 3 (STAT3) as multicompartmental and reciprocal signaling hub that integrates these inflammatory, metabolic, and stromal signals across multiple cellular compartments. In this review, we examine how STAT3 contributes to tumor–microenvironment communication in these three malignancies, with particular emphasis on the interplay between tumor metabolism and immune regulation. We also discuss emerging therapeutic strategies targeting STAT3 and highlight the challenges associated with disease heterogeneity, biomarker development, and patient stratification that must be addressed for successful clinical translation.