Recent Advances in Understanding the Endometrial Cancer Tumor Microenvironment

Endometrial cancer (EC) incidence is rising globally, yet therapeutic progress has lagged behind other solid tumors, in part due to the complexity and heterogeneity of the tumor microenvironment (TME). The TME in EC comprises immune cells, cancer-associated fibroblasts (CAFs), endothelial and perivascular cells, adipocytes, extracellular matrix (ECM), and a dynamic network of cytokines, chemokines, and metabolic cues that collectively shape tumor initiation, progression, immune escape, and therapeutic response. Recent multi-omic and spatially resolved profiling has begun to elucidate how molecular subtypes of EC (e.g., POLE-mutated, MSI-H/dMMR, copy-number low, copy-number high/serous-like) exhibit distinct microenvironmental architectures and immune ecologies, with implications for risk stratification and precision therapy.There is also a growing evidence suggesting that the female genital tract microbiome plays an important role in the pathogenesis of endometrial cancer. Microbial dysbiosis may influence tumor development by many various ways, including modulation of local inflammation processes, estrogen metabolism, and immune response. Understanding the interplay between the microbiome and endometrial cancer could lead to identification of new potential risk factors, novel diagnostic opportunities as well as therapeutic, and maintenance approaches.This Research Topic invites contributions that deepen mechanistic and translational insight into EC TMEs. Areas of interest include: • immune contexture and functional states of T cells, NK cells, myeloid populations, and tertiary lymphoid structures; • stromal remodeling, CAF phenotypes, and ECM mechanics as determinants of invasion and therapeutic resistance; • tumor–vasculature crosstalk, hypoxia, and angiogenic signaling; • metabolic reprogramming (glucose, lipid, and one-carbon metabolism), adipose–tumor interactions in the uterine milieu, and their impact on immune fitness; and • microbiome, hormonal, and reproductive cues that modulate the TME across the endometrial continuum, including precursor lesions and recurrent disease. • molecular and cellular mechanisms leading to tumorigenesis, tumour growth, and its progression;• molecular biomarkers for disease monitoring;• novel immunotherapeutic approaches based on molecular subtypes• advances in microbiome research, encompassing mechanistic insights and translational applicationsWe particularly welcome studies leveraging spatial transcriptomics/proteomics, single-cell technologies, multiplex imaging, and computational modeling to map cellular neighborhoods and signaling niches.Translational submissions addressing therapeutic vulnerabilities are strongly encouraged, including biomarkers of response or resistance to immunotherapy (checkpoint blockade, bispecifics), anti-angiogenic and anti-stromal strategies, combinations that recondition “cold” tumors, and rational approaches informed by TME subtype. Work exploring the interface of standard treatments (surgery, radiotherapy, systemic therapy) with microenvironmental adaptation and minimal residual disease is also of interest, as are preclinical models that faithfully recapitulate the EC TME, including organoids, patient-derived xenografts, explants, and ex vivo immune co-cultures.By integrating mechanistic biology with advanced profiling and therapeutics, this collection aims to refine our understanding of endometrial cancer ecosystems and accelerate the development of microenvironment-informed interventions. Submissions may include original research, brief reports, methods, and comprehensive reviews that collectively chart the path from TME characterization to clinically actionable strategies.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public omics databases that are not supplemented by relevant functional validation (clinical cohort or biological validation, in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Bartłomiej Barczyński, Rudy Leon De Wilde, Karolina Fraszczak Source: https://www.frontiersin.org/research-topics/75997/recent-advances-in-understanding-the-endometrial-cancer-tumor-microenvironment