Deciphering the tumor microenvironment in esophageal cancer: cellular heterogeneity and functional crosstalk

Esophageal cancer (EC) is a highly prevalent malignant tumor worldwide, with a particularly high incidence in regions such as Asia. The poor prognosis of EC is attributed mainly to late detection, high invasiveness, and limited treatment efficacy. Growing evidence has revealed a close association between the adverse outcomes of EC and the tumor microenvironment (TME). This review comprehensively summarizes advances made from 2020 to 2025 in understanding the TME of EC based on single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. First, we illustrate the heterogeneity of major cellular components within the TME, with a focus on subtype classification, dynamic phenotypic changes, and the clinical significance of T cells, B cells, tumor-associated macrophages (TAMs), dendritic cells (DCs), and cancer-associated fibroblasts (CAFs). Then, we highlight the functional crosstalk mechanisms underlying anti-tumor immunity and the dual regulatory role of tertiary lymphoid structures (TLS) in the TME. Finally, we address current challenges in EC TME research, including inconsistencies in cell subtype classification, significant inter-patient heterogeneity, and incomplete understanding of cellular crosstalk signaling networks. We aim to provide a foundation for further mechanistic exploration of the EC TME and to support the development of novel therapeutic strategies.