The Tumor Immune Microenvironment in Endometrial Cancer: Composition, Molecular Subtypes, and Therapeutic Implications

Abstract

Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide. Classified as an immunologically “cold” tumor, EC exhibits a tumor immune microenvironment (TIME) that critically influences tumor initiation, progression, and therapeutic response. This review systematically examines the composition and functional characteristics of the TIME in EC, including the distribution and phenotypic states of major immune cell populations—such as tumor-associated macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes—as well as key non-immune components, including cancer-associated fibroblasts and cytokines. We further elucidate mechanisms of immune suppression, primarily mediated by the programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway and the consequent immune evasion processes. Integrating molecular classifications of EC, we analyze the immunogenicity of distinct TIME subtypes and their differential responses to immunotherapy. Recent advances in immune-based therapeutic approaches are also highlighted, encompassing immune checkpoint blockades, adoptive cell therapies, cancer vaccines, and combination regimens with chemotherapy or molecularly targeted agents. Collectively, this review emphasizes the intricate complexity of TIME in EC, evaluates the strengths and limitations of current immunotherapies, and offers forward-looking perspectives to guide future research and clinical translation, particularly in the identification of novel therapeutic targets and the advancement of precision oncology strategies.