A narrative review of the value of immunoinflammatory markers in the prognosis of endometrial carcinoma

Introduction

Endometrial cancer (EC) ranks as the sixth most common gynecological cancer worldwide, with both incidence and disease-related mortality rates on an upward trajectory. Over the past decade, the incidence has been steadily increasing by approximately 1.3% annually, and the number of cases among women under 50 has been on the rise (1,2). EC can be classified into type I and type II based on the stage of development. Type II EC, in contrast to type I, encompasses rare pathological forms such as endometrial serous carcinoma, clear cell carcinoma, and carcinosarcoma. These tumors are highly malignant, poorly differentiated, and often exhibit negative or low expression of estrogen and progesterone receptors, resulting in a dismal prognosis (3). Furthermore, due to racial disparities, geographical differences, and economic conditions, significant variations exist in the incidence, mortality, and prognosis of EC (4,5). The majority of patients diagnosed with EC are in the early stages of the disease and have a favorable prognosis (6,7). Nevertheless, a subset of low-grade, early-stage, well-differentiated ECs still experience unexpected recurrence and unfavorable outcomes. For women with recurrent or advanced disease, as well as those diagnosed with clinically aggressive histological subtypes (such as the serous histotype), the clinical outcomes deteriorate significantly (8,9). Despite this, reliable prognostic biomarkers for EC remain scarce (10). Currently, The Cancer Genome Atlas (TCGA) has substantially revealed the biological heterogeneity underlying EC prognosis. However, it has limited practical utility in the precise management of EC patients. Further exploration of molecular biomarkers with clinical significance for EC prognosis is crucial for the timely implementation of effective and personalized adjuvant therapies while minimizing the toxic side-effects associated with over-treatment (11).

The immune-inflammatory response associated with cancer is increasingly recognized as a fundamental mechanism in tumorigenesis. A growing body of evidence suggests that it plays a pivotal role in tumor growth, progression, invasion, and metastasis (12). Virchow first observed leukocytes in tumor tissues in 1881, postulating a connection between immune-inflammation and cancer. Some scholars attribute this association to the inflammation induced by the tumor and the host’s immune response. The immune-inflammatory response is central to the tumor microenvironment. Inflammatory cells, including neutrophils, lymphocytes, monocytes, and platelets, are crucial components of the tumor-induced systemic inflammatory response. The release of damage-associated molecular patterns (DAMPs) during tumor necrosis leads to immune suppression within the tumor microenvironment and recruits diverse inflammatory cells, thereby restricting the biological activity of DAMPs (13). The clinical significance of these blood-derived immune-inflammatory indicators in female malignancies is attracting increasing attention. Research has shown that a high neutrophil-to-lymphocyte ratio (NLR) is indicative of a poor prognosis in EC patients (14).

This review aims to critically synthesize the current evidence on the prognostic utility of immunoinflammatory markers in EC. We will systematically analyze the strength of association for peripheral blood indices and tumor immune microenvironment (TIME) features with survival outcomes, while explicitly detailing study methodologies, confounder adjustment, and clinical endpoints. Furthermore, we will discuss the integration of these markers into predictive models, their role in guiding immunotherapy, current limitations related to standardization and confounding, and future directions for clinical translation. We present this article in accordance with the Narrative Review reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0011/rc).

Methods

We conducted a comprehensive narrative review. To identify relevant studies, we searched the PubMed and Web of Science databases for articles published from January 1, 2000 to July 31, 2025 using a combination of the following keywords and MeSH terms: “endometrial neoplasms”, “prognosis”, “biomarkers”, “neutrophils”, “lymphocytes”, “tumor microenvironment”, “tumor-infiltrating lymphocytes”, and “immune checkpoint inhibitors”. The search was not restricted by study design to capture all relevant evidence, but emphasis was placed on clinical studies reporting survival outcomes. The search strategy is summarized in Table 1.

To clearly define the research question and standardize the scope of literature screening for this narrative review, we first established a Population-Exposure-Comparison-Outcome (PECO) framework (Table 2)—with exposure replacing intervention to adapt to the characteristics of prognostic biomarker research rather than interventional clinical research. Inclusion criteria focused on studies investigating the association between predefined immunoinflammatory markers (peripheral blood indices or TIME features) and clinical outcomes [overall survival (OS), progression-free survival (PFS), disease-free survival (DFS)] in EC patients. Exclusion criteria included non-original research, case reports, and conference abstracts. Given the narrative nature of this review, a formal systematic screening process with a PRISMA flow diagram was not employed; instead, we focused on a critical synthesis of key and representative studies that aligned with the PECO framework to address our clinical question.

Prognostic value of peripheral blood immune-inflammatory indices

Currently, commonly used clinical inflammatory prognostic indicators, such as NLR, platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), which are readily accessible from peripheral blood, have been reported as independent prognostic indicators for various tumors, including esophageal squamous cell carcinoma, pancreatic cancer, liver cancer, and bladder cancer. Higher levels of these inflammatory prognostic indicators are associated with a poor prognosis (15-17). The clinical significance of these blood-derived immune-inflammatory indicators in female malignancies is attracting increasing attention. Routine blood count-derived indices offer a cost-effective and minimally invasive window into the host’s systemic inflammatory state.

NLR and PLR

Pretreatment elevation of NLR and PLR has been consistently linked to adverse clinicopathological features and worse survival in EC. Crucially, several studies have demonstrated their independent prognostic value after adjusting for key confounders.

Haruma et al. [2015], in a study of 297 EC patients, found that a preoperative NLR >2.5 [determined by receiver operating characteristic (ROC) analysis] was significantly associated with shorter DFS and OS. Multivariate analysis confirmed NLR as an independent predictor for mortality [hazard ratio (HR) =3.318, 95% confidence interval (CI): 1.154–9.538; P=0.026], even after adjustment for stage and grade (18). A separate retrospective analysis of 197 patients demonstrated that higher NLR was an independent predictor of lymph node metastasis [odds ratio (OR) =5.98; 95% CI: 1.09–32.6; P=0.039] alongside lymphovascular invasion (19). These studies collectively demonstrate that immune-inflammatory indicators are of great value in reflecting the prognosis of EC (Table 3).

SII

SII (platelets × neutrophils/lymphocytes), a new inflammatory marker based on neutrophil, platelet, and lymphocyte counts, is non-invasive and cost-effective, helping to identify high-risk patients. Compared with established inflammatory markers such as NLR, PLR and MLR in hepatocellular carcinoma, various gastrointestinal malignancies, small-cell lung cancer, and multiple gynecological malignancies, SII can comprehensively reflect the balance between the host’s immune and inflammatory states, with higher predictive accuracy for prognosis. It is an independent prognostic factor for multiple tumors (20). Multiple clinical studies have shown that SII levels are closely related to the staging and grading of EC (21). In patients with early-stage EC, SII values are relatively low, while as the tumor progresses to the advanced stage, SII levels show a significant upward trend. However, previous studies exhibit substantial methodological heterogeneity, which severely limits the application of SII in cross-study comparisons and clinical translation. For example, Matsubara et al. [2021], Holub et al. [2020], Huang et al. [2021], and Njoku et al. [2022] reveal that three studies evaluated pre-treatment SII but with variable time windows: one measured SII within 1 month before neoadjuvant chemotherapy, and two within 3 months before surgery. Despite overlapping pre-treatment definitions, their prognostic conclusions diverged: reported high pre-treatment SII correlated with both worse OS (HR =2.89; 95% CI: 1.56–5.35; P=0.001) and DFS (HR =2.17; 95% CI: 1.23–3.82; P=0.008), confirmed associations with OS (HR =1.96; 95% CI: 1.16–3.30; P=0.012) and PFS (HR =1.71; 95% CI: 1.11–2.62; P=0.014), while only linked pre-treatment SII to OS (HR =2.2; 95% CI: 1.1–4.6; P=0.025) but not PFS (HR =1.4; 95% CI: 0.7–2.7; P=0.312). In contrast, exclusively analyzed postoperative SII (1 month after resection) and identified it as a stronger OS predictor (HR =8.735; 95% CI: 1.447–51.646; P=0.017) than pre-treatment SII in other cohorts—highlighting ambiguity about whether baseline (pre-treatment) or treatment-modified (postoperative) inflammation better reflects long-term EC prognosis (21-24). The determination of cut-off values for the SII varies significantly across studies, and there is no consensus on the optimal method, resulting in inconsistent threshold setting. For instance, some studies have employed ROC curve analysis (which is data-driven and outcome-specific) to derive different cut-off values, while others have only reported the area under the curve (AUC) for OS without explicitly providing the corresponding threshold. Multivariate Cox models differ in the inclusion of EC-specific prognostic confounders—particularly tumor stage, histological grade, and lymphovascular space invasion (LVSI)—all of which are known to independently influence EC outcomes. The study by Matsubara et al. (22) achieved the most comprehensive adjustment by incorporating these three factors, confirming the independence of SII from stage, grade, and LVSI. This variability raises concerns about residual confounding: for example, LVSI increases the risk of EC recurrence by 2–3 fold, which may inflate or mask the true prognostic effect of SII in these studies. To resolve these inconsistencies, future research should: (I) standardize SII measurement to a pre-specified time point (e.g., 2 weeks before definitive treatment or 1 month postoperatively); (II) prioritize ROC curve analysis with internal/external validation for cut-off determination (and uniform unit reporting); (III) consistently include stage, grade, and LVSI in multivariate models. Such standardization will validate SII as a reproducible prognostic marker, enabling its integration into EC risk stratification protocols (Table 4).

Other indices and novel markers

Cytokines, as “messengers” for intercellular signal transmission, play a crucial role in the immune-inflammatory regulatory network. In many types of cancer, inflammatory factors are closely related to the occurrence, development, and prognosis of tumors, which has been confirmed in numerous tumors (25). Inflammation is a key feature of cancer and plays a crucial role in regulating the tumor microenvironment. There have been many research reports on the interleukin (IL) family. Among them, IL-2, IL-7, IL-12, IL-15, IL-24, and IL-28 have significant anti-tumor activities (26). In the tumor microenvironment, an elevated IL-6 level often indicates an exacerbation of the inflammatory response and an acceleration of tumor progression. Wang et al. found that the protein level of IL-37 in EC cells was significantly reduced, and the activated and mature IL-37b, namely IL-37bΔ1-45, could inhibit the migration and invasion of EC cells by targeting and regulating the Rac1/nuclear factor-κB (NF-κB)/MMP2 signaling pathway (27). Based on the cancer clinical data from TCGA and the Tumor Immune Estimation Resource (TIMER), Tong et al. found that the expression level of IL-9 was upregulated in multiple cancers, including EC. By recruiting 143 patients with EC to establish an IL-9-patient prognosis nomogram, they further found that a high expression level of IL-9 was associated with a good prognosis in patients with EC (28). Thus, it can be seen that some ILs in the IL family, such as IL-2 and IL-15, have significant anti-tumor abilities. However, there is currently a lack of multicenter clinical research data on their application in the diagnosis and treatment of EC (29).

Toll-like receptors (TLRs) belong to the IL-1 receptor family (30). Their main function is to initiate a signal transduction cascade to enhance gene expression. Due to the continuous activation of TLRs by pathogen-associated molecular patterns (PAMPs), epithelial cells in the female reproductive system are prone to tumor transformation. Tumor neovascularization is mainly induced by vascular endothelial growth factor (VEGF), which is related to TLR signaling. Overexpression of VEGF in tumor cells promotes tumor development and metastasis. For example, after TLR4 on the surface of EC cells is activated, it can upregulate the secretion of IL-6, IL-8, etc. through the myeloid differentiation primary response 88 (MyD88)-dependent pathway, enhancing the invasiveness of tumor cells. In addition, extracellular matrix-degrading enzymes in the inflammatory microenvironment, such as members of the matrix metalloproteinase (MMP) family, are upregulated in response to inflammatory factor stimulation. They can degrade the extracellular matrix, break down tissue barriers, and help tumor cells break through the basement membrane and infiltrate into surrounding tissues and metastasize to distant sites, making the patient’s prognosis difficult. It has been found that IL-6 promotes the growth of EC through an expanded autocrine regulatory loop, and the ERK-NF-κB pathway is a key mediator of IL-6 production (31).

Tumor necrosis factor-α (TNF-α) is mainly produced by mononuclear macrophages. Under normal circumstances, its content in peripheral blood is extremely low. Once the body is invaded by inflammatory factors, its level will rise rapidly. By activating the NF-κB signal pathway, it induces the expression of multiple inflammation-related genes, triggering an inflammatory cascade reaction. At the same time, it is also involved in the apoptosis regulation of tumor cells, having a profound impact on the occurrence and development of tumors. Continuous inflammatory stimulation prompts tumor cells and surrounding stromal cells to secrete a large number of cytokines and chemokines, such as IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP-1). These molecules attract inflammatory cells such as mononuclear macrophages and neutrophils to the tumor site, forming an inflammatory infiltration focus (32). Among them, TNF-α not only activates the NF-κB signal pathway, upregulates the expression of anti-apoptotic proteins in tumor cells, and inhibits tumor cell apoptosis but also promotes the secretion of tumor VEGF, driving tumor angiogenesis and providing sufficient nutrient supply and metastasis pathways for tumor cells (33). IL-6, on the other hand, enhances the proliferation, migration, and invasion abilities of tumor cells by activating the signal transducer and activator of transcription 3 (STAT3) signal pathway. At the same time, it induces the expansion of myeloid-derived suppressor cells (MDSCs), which further inhibits the body’s immune function, forming a vicious cycle that accelerates tumor progression and worsens the patient’s prognosis.

The NLR family pyrin domain containing 3 (NLRP3) inflammasome can promote cancer cell apoptosis by activating pyroptosis, showing anti-cancer potential, and the inflammasome plays a central role in this process. EC is closely related to long-term inflammatory stimulation. On the one hand, the inflammasome can accelerate the development of EC through specific inflammatory signal pathways. On the other hand, it can also inhibit cancer progression by inducing cancer cell pyroptosis.

Recent evidence points to osteopontin (OPN) as a potentially significant inflammatory mediator in EC. Aquino et al. [2025] systematically reviewed OPN’s role, noting its overexpression in EC is linked to proliferation, invasion, metastasis, and poor prognosis, suggesting it as a therapeutic target and prognostic marker (34).

Considerations of bias and confounding

The interpretation of peripheral blood indices requires caution due to significant confounding. Levels of NLR, PLR, and SII can be acutely influenced by non-oncological conditions such as active infection, chronic inflammatory diseases, corticosteroid use, obesity/metabolic syndrome, and recent surgery (e.g., postoperative neutrophil peaks) (35,36). Furthermore, the optimal prognostic cut-off values vary considerably across studies (e.g., NLR cutoffs ranging from 1.9 to 4.0), driven by differences in population, assay methods, and statistical approaches (ROC vs. median). Future prospective studies must standardize pre-analytical conditions, establish validated cut-offs, and rigorously adjust for these confounders in multivariate models to confirm their independent utility.

Prognostic and predictive significance of the TIME

In the tumor immune-inflammatory microenvironment, the composition and functional significance of the dynamic equilibrium among immune cell subsets are of paramount importance, serving as the cornerstone for maintaining the body’s immune homeostasis. The body is equipped with a vast array of immune cells, including T lymphocytes (37), B lymphocytes (38), and various phagocytes, which collaborate to regulate the body’s immune balance. Tumor-associated immune cell subsets play a critical role in the onset, development, and prognosis of EC. The density, location, and functional state of immune cells within the TIME provide a direct reflection of the host’s anti-tumor immune response.

T lymphocytes

T lymphocytes can be classified into two subsets: CD8⁺ T cells and CD4⁺ T cells. CD4⁺ T lymphocytes can be further categorized into several subtypes, such as T-helper cell 1 (Th1), T-helper cell 2 (Th2), and regulatory T cell (Treg), based on the distinct cytokines they secrete (39). Th1 cells primarily secrete cytokines like interferon-γ (IFN-γ), which activate macrophages, enhance the body’s cellular immune function, and combat tumor cells, thereby contributing to a better prognosis for patients. Th2 cells, on the other hand, mainly secrete IL-4, IL-10, etc., focusing on promoting the humoral immune response and playing a role in allergic reactions and anti-inflammatory processes. In certain circumstances, Th2 cells may promote tumor growth. If they dominate the tumor microenvironment, they may trigger tumor progression and impact the prognosis unfavorably (40). A Th1-dominant microenvironment (high IFN-γ) correlates with better outcomes, whereas a Th2-skewed response (high IL-4, IL-10) is linked to immunosuppression and poorer prognosis (41).

Treg cells are an immunosuppressive subset of CD4⁺ T lymphocytes, characterized by the expression of forkhead box P3 (FOXP3), CD25, and CD4. They regulate the physiological and pathological responses of the immune system, safeguarding the body from excessive immune reactions. However, in the tumor microenvironment, the over-activation of Treg cells can impede the body’s anti-tumor immunity, creating a conducive environment for the growth and metastasis of tumor cells. The quantity of Tregs cells or the expression level of their associated markers (such as FOXP3) serves as an important evaluation criterion. When the number of Tregs cells increases or FOXP3 is highly expressed, it indicates enhanced immunosuppression, making it easier for tumor cells to evade the body’s immune system, leading to tumor progression and an elevated risk of recurrence for patients (42,43). High infiltration of FOXP3⁺ Tregs is a strong independent adverse prognostic factor, associated with higher grade, stage, and reduced survival. In the EC microenvironment, Treg cells are frequently found to be abnormally elevated. They secrete immunosuppressive factors such as IL-10 and transforming growth factor-β (TGF-β), inhibiting the anti-tumor activities of CD8⁺ T lymphocytes and natural killer (NK) cells, enabling tumor cells to escape immune surveillance (44). Studies have revealed that the proportion of Treg in total CD4⁺ T cells in the peripheral blood of EC patients is significantly higher than that of healthy women, which is conducive to the malignant progression of tumors (45). EC cells may interact with CD4⁺ Treg cells via TNF-inducible T-cell costimulator (ICOS), inducing an immunosuppressive microenvironment, suggesting that blocking the binding of TNF-ICOS could be a potential therapeutic target for EC (46). Kolben et al. (38) discovered that co-culturing CD4⁺ CD25⁺ Treg with EC cells can directly enhance the proliferation, migration, and invasion capabilities of EC cells.

CD8⁺ T lymphocytes, as cytotoxic T lymphocytes (CTLs), can directly recognize and eliminate tumor cells. The fluctuations in their activity and number are directly correlated with the effectiveness of tumor immune surveillance (47). When the number of CTL is sufficient and their activity is robust, they can significantly impede the growth, proliferation, and metastasis of tumor cells. In immune-inflammation-related prediction models, if the relevant indicators reflecting the activity or number of CTL are favorable, such as normal secretion levels of specific cytokines, it often portends a better prognosis for patients (48). Studies have shown that compared to adjacent normal endometrium, the number of CD8⁺ T cells in EC increases. Nevertheless, the expression of granzyme A (GZMA), granzyme B (GZMB), and programmed death receptor 1 (PD-1) in CD8⁺ T cells from tumor tissues is significantly lower than that in adjacent normal endometrial tissues, and their cytotoxic killing ability against target cells is markedly reduced (49). In EC, the proportions of naive CD8⁺ T cells and CD8⁺ CTL in CD8⁺ T cells are significantly diminished, while the proportion of exhausted CD8⁺ T cells is augmented (50). Overall, a high overall density of tumor-infiltrating CD8⁺ T cells is typically associated with better OS and PFS. However, their functional state (such as exhaustion markers like PD-1) is critical; a significant proportion of exhausted CD8⁺ T cells can counteract their positive prognostic effect.

Tumor-associated macrophages (TAMs)

EC TAMs are predominantly the M2-like, pro-tumor phenotype. M2-type macrophages, conversely, tend to promote tumor angiogenesis, tissue remodeling, and immunosuppression, facilitating the proliferation, invasion, and metastasis of tumor cells (51,52). High overall TAM density (CD68⁺/CD163⁺) correlates with advanced stage, lymph node metastasis, and shorter OS (1,53). M2 TAMs promote metastasis via mechanisms like CCL18 secretion to induce EMT. Their prognostic impact interacts with molecular subtypes; for example, with the advent of the molecular classification of EC, the infiltration degree of programmed death-ligand 1 (PD-L1)⁺CD68⁺ macrophages in the tumor parenchyma and stroma of the TP53 mutation subtype is higher than that of other subtypes, accompanied by a substantial distribution of CD8⁺ PD-1⁺ T cells in the stroma, indicating the presence of an immunosuppressive microenvironment in this molecular subtype (53).

NK cells

NK cells are a type of innate immune cell with cytotoxicity comparable to that of CD8⁺ CTL and are also crucial anti-tumor effector cells (47). In EC, the reduced number and functional inhibition of NK cells (e.g., high expression of inhibitory receptors like TIGIT and TIM-3) reflect impaired immune surveillance, which is typically associated with poorer disease control (54). Research indicates that the reduction of chemokines (CXCL12, CCL27) and cytokines (IL-1, IL-6) in the microenvironment leads to the inhibition of the recruitment and killing ability of NK cells to the tumor tissue (55). NK cells promote tumor cell apoptosis and inhibit tumor cell proliferation and angiogenesis through antibody-dependent cell-mediated cytotoxicity and the secretion of IFN-γ, fulfilling an anti-tumor protective function (56). This indicates that the number of NK cells in EC tumor tissues is reduced, their function is inhibited, and their anti-tumor ability is significantly compromised.

Immune checkpoints and molecular context

Immune checkpoint inhibitors (ICIs) currently represent the most emblematic form of immunotherapy in clinical practice. By blocking immune-checkpoint molecules, ICIs can activate the body’s immune system, thereby eradicating tumor cells (57). ICIs primarily consist of two categories: one is inhibitors targeting the PD-1 and PD-L1 pathways, and the other is inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). PD-1/PD-L1 is the most prevalent immune checkpoint identified in T lymphocytes thus far (58). In 2022, the annual meetings of the American Society of Clinical Oncology and the European Society for Medical Oncology updated the latest data of the GARNET study. The condition of 45.5% of patients with deficient mismatch repair (dMMR) improved after treatment with dostarlimab, once again validating the efficacy of dostarlimab in the treatment of EC (59,60). Atezolizumab, a human-derived IgG1 monoclonal antibody, can block the immune escape of tumor cells by impeding the binding of PD-1 and PD-L1, thereby exerting an anti-tumor effect. It can inhibit tumor angiogenesis by blocking the VEGF receptor and achieve an anti-inflammatory effect by suppressing the infiltration and activation of inflammatory cells. A multicenter study found that, following treatment with atezolizumab, the objective response rate of patients with recurrent EC reached 13.3%, and the adverse reactions were relatively mild, mostly grade 1 or 2 (61). Avelumab, a fully humanized PD-L1 inhibitor, can prevent tumor cells from evading the anti-tumor response of immune cells by binding to PD-L1 and activate T cells to partake in tumor killing. A clinical study found that, after treatment with the PD-L1 inhibitor avelumab, the objective response rate and 6-month PFS rate of advanced EC patients who had received previous treatment were 26.7% and 40%, respectively. This indicates that avelumab has a positive impact on the treatment of advanced EC patients (62). PD-L1 expression on tumor or immune cells is not only a prognostic marker but also a predictive biomarker for response to ICIs, particularly in mismatch repair-deficient (MMRd) and POLE-mutant subtypes (59,63). Other checkpoints like lymphocyte activation gene-3 (LAG-3) and TIM-3 are also expressed in EC and represent potential therapeutic targets (64,65).

Integrated prognostic models and future perspectives

Given the complexity of EC, combining multiple markers into integrative models shows superior predictive power over single parameters. Models incorporating immune gene signatures (e.g., Tregs-related risk signature), radiomic features from imaging, and peripheral blood indices with clinical factors [International Federation of Gynecology and Obstetrics (FIGO) stage, grade] are under development (66,67). These models aim to move beyond association towards personalized risk prediction.

Key limitations of current evidence include the retrospective nature of most studies, heterogeneity in biomarker measurement and cutoff definitions, and insufficient adjustment for confounders. Future directions require: (I) prospective validation of the most promising markers; (II) standardization of assays [e.g., for tumor-infiltrating lymphocytes (TILs) scoring] and timing (pretreatment); (III) dynamic monitoring of markers during therapy; and (IV) integration with molecular classification (TCGA) to develop truly precision medicine approaches.

Conclusions

This paper has comprehensively explored the value of immune-inflammatory markers in predicting the prognosis of EC. Evidently, immune-inflammatory markers are intricately linked to the onset and progression of EC. They play a crucial role in predicting tumor recurrence, metastasis, and evaluating the survival outcomes of patients. In terms of the relationship between inflammation and tumorigenesis, the levels of immune-inflammatory markers increase in a chronic inflammatory environment. This persistent inflammation stimulates abnormal proliferation of endometrial cells, thereby altering the tumor microenvironment. Regarding the promotion of tumor cell proliferation and invasion, immune-inflammatory markers affect the biological behavior of tumor cells by activating relevant signal pathways and upregulating molecules associated with invasion and metastasis. In the aspect of immune regulation, immune-inflammatory markers suppress the body’s anti-tumor immune response, allowing tumor cells to evade immune surveillance. Immunoinflammatory markers-from readily available peripheral blood indices to detailed TIME characteristics-offer valuable layers of prognostic and predictive information for EC. Evidence suggests that elevated NLR, PLR, SII, high Treg/M2 TAM infiltration, and low CD8⁺ T cell activity are generally associated with more aggressive disease and worse survival. However, their translation into clinical practice is hampered by methodological inconsistencies and confounding influences. Future rigorous, prospective studies focused on standardization and integration into multifactor models are essential to realize their potential in improving risk stratification and guiding personalized treatment decisions for patients with EC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0011/rc

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0011/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0011/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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