Endometrial cancer (EC) is the third most common malignancy in women worldwide, with an estimated 420,000 new cases diagnosed annually. EC accounted for approximately 2.1 % of new cases and 1.0 % of cancer deaths in 2022 (Bray et al., 2024). Since 2008, the global incidence of EC has increased by 21 %, which is due to increased life expectancy and obesity rates (Makker et al., 2021).

Based on the SEER database, 18 % of newly diagnosed EC patients have regional lymph node invasion, and 11 % show distant metastasis; for distant metastasis patients, their 5-year overall survival rate has significantly decreased to 19.4 % (SEER, 2025). Previously, therapeutic options for EC patients with advanced or recurrent disease were limited to mainly chemotherapy, which had poor efficacy after first-line treatment. In 2013, the Cancer Genome Atlas (TCGA) Project proposed a novel molecular classification for EC based on genomic alterations. The four molecular subtypes include POLE exonuclease domain mutations (POLEmut), MMR deficiency (dMMR), p53 abnormal (p53abn), and no specific molecular profile (NSMP) (Jamieson and McAlpine, 2023). The TCGA classification has transformed EC management, which facilitated the development of new therapies. Across all studies, the dMMR subgroup showed an objective response rate (ORR) of approximately 50 % to immunotherapy (Marín-Jiménez et al., 2022). The elevated expression of the programmed cell death 1 (PD-1) receptor and its ligands (PD-L1), with the high tumor mutational burden (TMB) in dMMR tumors, suggests their potential responsiveness to anti PD-1/PD-L1 therapies (Le et al., 2017, Mamat @ Yusof, M. N. et al, 2023, De Felice et al., 2019). Building on these data, the 2025 ESGO-ESTRO-ESP guideline formally positions immune-checkpoint inhibitors (ICIs) as the first-line treatment for advanced or recurrent EC patients (Concin et al., 2025, Moore et al., 2025). For dMMR EC patients, an ICI (eg, dostarlimab, durvalumab, or pembrolizumab) should be recommended with chemotherapy, which is followed by single-agent ICI for maintenance therapy. For non-dMMR EC patients, standard chemotherapy ± an ICI can be considered, with subsequent maintenance therapy using an ICI ± a PARP inhibitor (Concin et al., 2025). Unfortunately, half of the patients failed to respond to ICIs (Marín-Jiménez et al., 2022). The current molecular classification could not adequately explain the differences in treatment efficacy. A comprehensive understanding of the mechanisms underlying treatment resistance in these patients is essential for identifying suitable candidates for immunotherapy and the delineation of novel targets for combination therapy or monotherapy.

During tumor progression, the tumor microenvironment (TME) is progressively reprogrammed from a tumor-suppressive to a tumor-promoting state (Hanahan, 2022). This switch may be driven by multiple mechanisms of immune evasion, such as reduced antigen presentation, secretion of immunosuppressive factors, and accumulation of immunosuppressive cells (Galassi et al., 2024). Single-cell transcriptomic analyses of EC samples consistently reveal an expansion of exhausted T cells (CD4 + Tex and CD8 + Tex) and regulatory T cells (CD4 + Treg), which further confirms the establishment of an immunosuppressive microenvironment (Ren et al., 2022, Ren et al., 2024). Importantly, immune infiltration and functional profiles differ markedly among and even within the TCGA molecular subtypes of EC, which underscores that the immunosuppressive TME is a key determinant of immunotherapy response (Dey et al., 2023). Immune evasion modulation plays important roles in the progression, recurrence, and resistance to the treatment of EC. In recent years, the reduction in antigen presentation, increase in secretion of immunosuppressive factors, and elevation of immunosuppressive cells are emerging mechanisms of immune evasion (Galassi et al., 2024). These findings provide us with numerous potential therapeutic targets to alleviate tumor immune evasion.

This narrative review systematically summarizes the latest mechanisms by which components of TME in EC induce immune evasion, integrates the progress of ICI combinations, and discusses the challenges and prospects of immunotherapy. The aim is to provide a comprehensive theoretical basis for basic research and clinical practice in this field.