Global research trends and focus on immunotherapy for endometrial cancer: a comprehensive bibliometric insight and visualization analysis (2012-2024)

Endometrial cancer (EC) is a malignancy originating from the uterine epithelium and is the most common gynecological cancer in developed countries, accounting for about 5.9% of all cancers in women (1, 2). Data show that early-stage cancer accounts for approximately 67% of EC cases, with a 5-year survival rate of 81% (3). Among patients diagnosed with metastatic disease, the survival rate is lower (5-year survival rate of 16%), the risk of recurrence is higher, and recurrences often occur outside the pelvis (4). The 5-year survival rate for patients with pelvic recurrences is 55%, but for those with recurrence outside the pelvis, this rate drops to 17% (5). The prognosis of extra-pelvic recurrent disease depends on factors such as disease distribution, molecular subtypes, age, performance status, previous treatments, and the time since the last treatment (4). Overall, various forms of advanced EC still present significant therapeutic challenges (6). Until recently, the treatment of advanced and recurrent EC has changed little, with chemotherapy remaining the mainstay, leaving a large unmet clinical need (7).

Like many other cancers, the tumor microenvironment plays a critical role in the progression of EC and its response to treatment (8, 9). This includes interactions between the tumor and the stroma, as well as between the tumor and infiltrating immune cells (10). In normal endometrium, immune cells play vital roles in defending against external pathogens, promoting fertilization, and supporting tolerance and maintaining pregnancy (11, 12). Certain subtypes of EC exhibit significant immune cell infiltration, suggesting that immunotherapy could be a potentially effective alternative or adjunctive therapy to surgery (8, 13). Therefore, research into immunotherapy for EC is of paramount clinical and practical significance.

The immune microenvironment of the normal endometrium is complex, multi-layered, and adaptable, with immune cell composition and function changing significantly across different stages of the menstrual cycle. Key immune cells include natural killer (NK) cells, dendritic cells, macrophages, T cells (CD4⁺ and CD8⁺), and B cells (14). NK cells are abundant in the endometrium, playing crucial roles in rejecting foreign matter, combating infections, and regulating immune tolerance during pregnancy. They eliminate infected and tumor cells by secreting cytokines such as interferon-γ, and help modulate immune responses to support placental formation and embryo survival (15, 16). Moreover, NK cells exert cytotoxic effects by releasing Granzyme B and Perforin. Perforin forms pores in target cell membranes, allowing Granzyme B to enter and induce apoptosis, eliminating tumors and infected cells (15). In the endometrium, this aids pathogen defense and immune surveillance, supporting uterine stability, infection prevention, and pregnancy success (16). Dendritic cells primarily function as antigen-presenting cells, initiating adaptive immune responses by activating T cells (17). Macrophages participate in local immune defense and are critical for maintaining immune tolerance during pregnancy, secreting cytokines that regulate the endometrial immune environment to prevent fetal rejection (18). T cells in the endometrium include regulatory T cells (Tregs) and effector T cells. Tregs maintain immune tolerance to prevent excessive immune responses against the fetus, while effector T cells recognize and eliminate pathogens (12). During menstruation, the proportion and activity of immune cells increase to clear damaged tissues and cells, while also controlling infections (8). Overall, the immune microenvironment of the endometrium plays a key role in balancing immune defense and tolerance across different physiological stages.

EC is one of the most common malignant tumors of the female reproductive system. It is generally classified into two major types: Type 1 and Type 2. These two types of EC differ significantly in their pathogenesis, clinical manifestations, prognosis, and treatment responses (19). Type 1 EC is typically associated with prolonged exposure to estrogen. It often arises from estrogen-dependent endometrial hyperplasia and is more common in premenopausal or postmenopausal women. Type 1 EC is usually low-grade and well-differentiated, with tumor cells resembling normal endometrial epithelial cells, resulting in a relatively good prognosis. This type of cancer is predominantly hormone-dependent and responds well to hormone therapy, contributing to a relatively favorable outcome. Hormone therapy is often used in the treatment of early-stage EC (20). Type 2 EC is estrogen-independent and typically occurs in older women. These tumors often develop without a clear foundation of endometrial hyperplasia and are characterized by higher malignancy and poorer prognosis. Type 2 tumors are often high-grade, poorly differentiated, and lack significant hormone dependence, exhibiting stronger invasiveness and metastatic potential (21, 22). Unlike Type 1, Type 2 EC typically shows poor response to hormone therapy, necessitating alternative treatments such as surgery, chemotherapy, or radiotherapy.

The immune microenvironment of EC changes significantly as the disease progresses, reflecting the invasiveness and aggression of the tumor. In early-stage (stage I) EC, the immune microenvironment is generally “milder,” with stronger local immune responses. Tumor-associated immune cells primarily include T cells, dendritic cells, and NK cells, all of which play essential roles in tumor recognition and clearance. In stage I EC, the immune system remains relatively effective at detecting and eliminating tumor cells, and the immune response is largely intact (23, 24). However, as the disease progresses into more advanced stages (stages II, III, and IV), the composition and function of immune cells within the tumor microenvironment undergo significant changes (25). As EC progresses, the tumor microenvironment gradually develops a hypoxic state, leading tumor cells to regulate metabolism by activating hypoxia-inducible factor-1α (HIF-1α) to adapt to adverse conditions. Meanwhile, lactate accumulation and alterations in glucose metabolism (the “Warburg effect”) not only provide a growth advantage for tumor cells but also suppress T cell function and promote the recruitment of immunosuppressive cells (26, 27). Additionally, the number of M2 macrophages, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) increases, suppressing anti-tumor immunity through the secretion of cytokines such as TGF-β and IL-10 (28). Moreover, the high expression of PD-L1 on tumor cells further weakens T cell activation, promoting immune evasion (29). Furthermore, tumor cells employ various mechanisms to induce immune tolerance, preventing the immune system from recognizing and effectively eliminating the tumor cells (30). In addition to immune evasion, tumor-associated fibroblasts (CAFs) also play a significant role in the immune microenvironment of EC. CAFs promote tumor growth, invasion, and metastasis by secreting growth factors and cytokines that further suppress immune responses (31, 32). As the disease progresses, the immune system within the tumor microenvironment becomes increasingly ineffective at counteracting the tumor, contributing to resistance to treatment and poor prognosis.

In recent years, immune therapy has gained significant attention in the research and treatment of EC. Immunotherapy is based on the idea of harnessing the body’s immune system to recognize and destroy tumor cells. Among the various immune therapies, immune checkpoint inhibitors, particularly PD-1/PD-L1 inhibitors, have emerged as a promising treatment strategy (33). The PD-1/PD-L1 pathway plays a critical role in immune evasion in many tumors, including EC (34). By blocking this pathway, PD-1/PD-L1 inhibitors can restore T cell function and enhance the immune response against tumors. In EC, especially in cases with high microsatellite instability (MSI-H) or defective mismatch repair (dMMR), immune checkpoint inhibitors have demonstrated promising clinical results (4). Studies have shown that high PD-L1 expression is often associated with MSI-H or dMMR endometrial cancer (4). These subtypes have a higher neoantigen load, making them more easily recognized by the immune system and therefore more responsive to immune checkpoint inhibitors (ICIs) (35).These patients typically have higher mutation loads and stronger immune responses, making them more sensitive to immune checkpoint inhibition. Several clinical trials have shown that PD-1/PD-L1 inhibitors significantly improve outcomes in these patients, leading to higher survival rates. In addition to immune checkpoint inhibitors, tumor vaccines, immune cell therapies (such as CAR-T cell therapy), and other immune-modulatory strategies are also under investigation, aiming to activate or enhance the immune system to better target and eliminate tumors (36, 37). Although CAR-T therapy has been successful in hematologic malignancies, its efficacy in solid tumors such as EC is limited by the suppressive effects of the tumor microenvironment (TME) (38). For example, immunosuppressive factors in the TME (such as TGF-β and IL-10), hypoxia, and tumor-associated fibroblasts (CAFs) collectively reduce the survival and cytotoxicity of CAR-T cells (38). Increasing research is exploring the combination of PD-1/PD-L1 inhibitors with other therapies, such as anti-VEGF agents, tumor vaccines, or metabolic interventions, to overcome the immunosuppressive TME and enhance the effectiveness of immunotherapy (3, 24, 39).

While immunotherapy remains an emerging field in the treatment of EC, ongoing basic research and clinical trials are expected to expand treatment options for patients, especially those with advanced or recurrent diseases who have limited responses to conventional treatments. As research progresses, immunotherapy could become a new breakthrough in the treatment of EC, improving patient prognosis and survival rates. Certainly, although researchers have made relentless efforts at the basic research level and proposed various innovative approaches to push their potential for clinical application, a considerable proportion of current immunotherapy strategies still face a lack of widespread, solid evidence of practical value, particularly with significant shortages in clinical settings. The profound barriers between basic research and clinical application highlight significant deficiencies in current research. Therefore, there is an urgent need for researchers in the molecular immune mechanisms of EC and novel immunotherapy strategies to overcome their own knowledge gaps, explore more avenues for collaboration, and find integration points that bridge geographical and disciplinary divides.

Currently, although some reviews have been conducted on the immune microenvironment and immunotherapy strategies for EC, they primarily focus on specific advancements, leaving other relevant aspects unexplored. Thus, there is a need to use specialized tools for a comprehensive analysis of literature in this field, providing researchers with multidimensional guidance and insights. Bibliometrics is a discipline that uses statistical and mathematical tools to analyze bibliographic data, studying the quantity, quality, structure, trends, and impact of academic publications (40, 41). It helps evaluate the development of academic achievements, journals, authors, institutions, and fields. By analyzing large volumes of literature, bibliometrics reveals trends in specific disciplines, allowing researchers to quickly grasp research hotspots and frontier issues (42, 43). It also helps assess academic influence through citation analysis, supporting academic evaluation and funding applications (29, 44). Additionally, bibliometrics uncovers research collaboration networks, identifies key collaborators, and promotes interdisciplinary cooperation. It assists researchers in selecting high-impact journals and aids publishers in evaluating their rankings and influence. Analyzing keywords and themes helps identify knowledge gaps, offering inspiration and guidance for future research directions (45).

The research progress in immunotherapy for EC has provided new molecular-level insights into changes in its immune microenvironment, while laying the foundation for targeted treatments or adjunctive therapies transitioning from basic research to clinical application. However, the varying immunotherapy responses at different stages of the tumor, especially the complexity of advanced and recurrent EC, pose significant challenges for researchers. Thanks to the rapid development of molecular biotechnology and the continuous discovery of emerging potential therapeutic targets, this field has been energized, particularly after 2012, with a large volume of related literature published in the past decade. Considering this, we conducted a novel bibliometric analysis of the literature on this topic, aiming to provide valuable insights into the current status and future research directions by using CiteSpace and VOSviewer—two widely recognized software tools in bibliometric analysis and network visualization (46–48). Given that our search strategy did not retrieve valid data prior to 2012, and papers published after September 2024 are still dynamic updating, we focused on analyzing literature published between 2012 and August 2024. Our goal is to analyze the global mainstream trends in this field by reviewing existing literature, identifying the countries, regions, institutions, journals, and authors that exhibit the highest productivity and influence, and determine emerging topics that will attract attention in future research within this field.

The immunotherapy of tumors has evolved from theoretical hypotheses to continuous refinement and breakthroughs in clinical applications. As early as 1909, Paul Ehrlich proposed the hypothesis that the immune system could recognize and eliminate tumor cells, laying the foundation for tumor immunology research (69). At the end of the 19th century, William B. Coley attempted to stimulate the immune system using bacterial toxins to treat cancer, marking the prototype of immunotherapy (70). In the 1960s, Burnet and Thomas introduced the “immune surveillance theory,” uncovering the mechanism of tumor immune evasion (71). In the 1970s, interleukin-2 (IL-2) and interferons were employed in cancer treatment, driving the development of non-specific immunotherapy (72). In 1997, the first monoclonal antibody for cancer treatment, rituximab, was approved, heralding a new era of targeted immunotherapy (73). Subsequently, drugs such as trastuzumab were widely applied to breast cancer and lymphoma (74). In-depth research on tumor antigens has led to the development of antigen-based vaccines. Key identification methods include gene expression analysis, proteomics, and immunohistochemistry for cancer-testis (CT) antigens, and whole-exome sequencing, bioinformatics, and immunological validation for neoantigens (75, 76). Researchers have used CT antigens as targets for tumor vaccines and developed personalized vaccines by identifying patient-specific neoantigens (77). These strategies have diversified tumor immunotherapy approaches, advancing the development of vaccines for malignant tumors like melanoma (77, 78). In 2011, ipilimumab, the first immune checkpoint inhibitor, was approved, followed by the emergence of PD-1/PD-L1 inhibitors, which significantly prolonged survival in various cancer patients and ushered in a new era of tumor immunotherapy (79). In 2017, CAR-T cell therapy was approved, bringing revolutionary progress in treating hematologic malignancies (38). In recent years, personalized vaccines based on neoantigens and strategies to regulate the tumor microenvironment have become research hotspots, driving immunotherapy toward precision medicine (80, 81).

This study conducted the first bibliometric analysis of EC immunotherapy-related literature published between 2012 and August 2024. Relevant papers were retrieved from the WoSCC database and analyzed using advanced software tools to construct and visualize bibliometric networks, deeply exploring research trends and development patterns in this field. The comprehensive application of these methods provides critical support for systematically understanding the research landscape and overall structure of this domain.

In general, the annual number of publications and citations are the most direct and effective indicators of scholars’ research focus in a particular field (82). According to our model analysis, in 2023, the number of publications in this field reached 152, while citations surpassed 3,623, both setting historical records for the field. This growth not only indicates that research in this area is receiving increasing attention but also reflects the growing interest and investment from the academic community in this topic. So far, the total number of citations for publications in this field has accumulated to 18,344, demonstrating the significance of these research results within the academic world. It is expected that with the emergence of more innovative findings, research in this field will reach new heights in 2024 and continue to grow. Further analysis reveals that over the past 13 years, both the annual publication volume and total citations have shown a significant upward trend, which not only affirms the progress of research in this field but also indicates the widespread attention and interest it has generated within both the academic and research communities (83).

Tracking the contributions of countries, institutions, and research teams provides valuable insights into the research trends in this field. Globally, China and the United States rank first and second in terms of publication volume, with 353 and 202 papers, respectively. This high publication output reflects a greater societal demand for related research in these countries compared to others. However, the United States stands out in terms of academic influence and innovation, acting as a leading pioneer in this field. In contrast, China should focus on enhancing its international accessibility through universities and research institutions to optimize research strategies and expand its influence. As globalization progresses, international collaboration is becoming increasingly important. The high academic influence of the United States is partly attributed to its effective cooperation with other countries, while collaboration between certain nations remains insufficient. Strengthening international partnerships could be an effective way to deepen research and applications in this field. Collaboration facilitates knowledge exchange, innovative ideas, and resource integration, ultimately advancing discipline.

Among the institutions with the highest publication volumes, the University of Texas Medical Anderson Cancer Center and Nanjing Medical University tie for first place, each with 26 papers. They are followed by Zhejiang University (22 papers), Fudan University (21 papers), and Leiden University (19 papers) (Figure 2B, Table 1). In terms of average citations per paper, Nanjing Medical University achieves 13.00 citations, while Leiden University and the University of Texas Medical Anderson Cancer Center lead with 53.84 and 39.69 citations, respectively. These findings align with national-level research outcomes. Thus, national-level studies must not only enhance research depth but also improve the international visibility of their publications to boost their impact. Additionally, results show that leading institutions, both domestic and international, remain the driving forces in academic research. Regarding funding agencies, the United States and Japan each account for 30% of the top 10 active funders, while China contributes 20% (Figure 3A and Table 2). However, the extent of international collaboration between institutions remains insufficient, with most partnerships occurring within national boundaries. This highlights the need for stronger international collaboration among institutions.

Through publication analysis, Gynecologic Oncology is identified as the most influential journal in the field, while Cancers, Frontiers in Oncology, Frontiers in Immunology, and Frontiers in Genetics are recognized as promising journals in the area of EC immunotherapy (Figure 3B and Table 4). Scholars from Leiden University, particularly the team of Bosse and Tjalling, lead in publications within the field with 18 papers, achieving the highest total citations (909) and total link strength (99). Notably, five of the top 10 authors are from this team, underscoring their sustained impact in this field (Table 5). Additionally, Gynecologic Oncology stands out with the highest total link strength (90,114) and citation count (2,456), further establishing its leading role in the field and providing critical references for future research and publication.

Highly cited papers reveal key research hotspots in the field. The paper by Talhouk et al. ranks first, with an average of 70.88 citations per year (Table 6). This study introduced the ProMisE molecular classification system based on The Cancer Genome Atlas (TCGA) and validated its feasibility and prognostic capability in a large EC cohort, providing a novel method for molecular classification and prognosis prediction in EC patients (51). The team led by Howitt focused on the application of immune checkpoint inhibitors in EC. Using TCGA data, they predicted neo-antigen loads and evaluated tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 expression in 63 EC patients. Their findings demonstrated that EC tumors with POLE mutations and MSI are associated with high neoantigen loads and TILs, along with PD-1/PD-L1 overexpression, making them promising candidates for PD-1-targeted immunotherapy (52). Leon-Castillo et al. conducted studies on high-risk EC patients, comparing the efficacy of combined chemoradiotherapy (CTRT) versus radiotherapy (RT) alone. Based on molecular classification, they evaluated the impact of chemotherapy on different subgroups and found that for p53abn tumors, CTRT significantly improved RFS, while POLEmut patients exhibited excellent RFS in both treatment regimens. They suggested future risk stratification and clinical trials should incorporate molecular classification to tailor treatments for specific subgroups (53). Overall, these highly cited research directions provide comprehensive guidance for the discipline’s frontiers and hotspots, holding significant reference value.

Research focal points can be effectively identified through the analysis of keywords and references, offering valuable insights into cutting-edge research directions and emerging trends. As illustrated in Figure 6A, references are grouped into nine distinct clusters. While earlier research predominantly explored areas such as “Micrometastases,” “Estrogen Receptor Alpha,” and “Endometrial Hyperplasia,” recent studies have shifted focus toward emerging topics, including “Ferroptosis-Related lncRNA,” “Tumor Mutation Burden,” and “PD-L1 Checkpoint Inhibition.” Subsequent biplot analysis (Figure 6B) reveals that articles in domains like Molecular Biology, Genetics, and Health, Nursing & Medicine are primarily cited by journals in Molecular Biology, Immunology, and Clinical Medicine. The growing citation links from medical and clinical sources highlight the increasing importance of interdisciplinary collaboration in advancing the transition from fundamental research to practical applications.

The analysis of reference citation bursts identifies articles that experienced notable surges in citations during specific periods, signaling rapid recognition and dissemination within the research community. The top 25 citation bursts (Figure 7B) indicate that the earliest burst occurred in 2014, while the most recent appeared in 2023. Moreover, keyword analysis offers further insights by identifying emerging topics and predicting future research trajectories. In this study, 141 critical keywords were identified and categorized into three main clusters. As shown in Figure 8A, these clusters include Cluster 1 (red nodes), focusing on Targeted Therapy and Checkpoint Inhibitors; Cluster 2 (green nodes), emphasizing the Tumor Immune Microenvironment and Immune Infiltration; and Cluster 3 (blue nodes), centered on Estrogen and Progesterone Receptors. Additional analysis (Figure 8B) highlights current research hotspots, such as “Checkpoint Inhibitors,” “m6A Modifications,” “Machine Learning,” “Cuproptosis,” and “Pyroptosis.”

To further examine emerging trends, we analyzed the top 25 keywords (Figure 8C), which primarily include “Tumor Microenvironment,” “Immune Infiltration,” and “Immune Checkpoint Inhibitors.” These keywords underscore their persistent relevance and focused attention within outbreak-related research, aligning closely with the findings of the citation burst analysis. The most highly cited papers in these three clusters are detailed in Table 7, offering a comprehensive overview and pioneering insights into this field. By examining the content and perspectives of these papers, researchers can gain a deeper understanding of current trends and valuable guidance for future investigations.

In recent years, immunotherapy research for EC has made significant progress, focusing on the tumor immune microenvironment (TME), molecular modifications, regulatory mechanisms, and the integration of emerging technologies. These advancements have introduced novel perspectives and strategies for EC treatment, particularly in unraveling tumor immune evasion mechanisms and enhancing immunotherapy efficacy (84).

The TME plays a critical role in the initiation, progression, and immunotherapeutic response of EC. Comprising tumor cells, immune cells, stromal cells, vasculature, and cytokine networks, the TME’s immune cell infiltration notably influences tumor immune evasion and therapy outcomes. Studies highlight the prominent roles of tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and dysfunctional effector T cells in the EC TME (85). These cells drive immune evasion through mechanisms such as the secretion of immunosuppressive cytokines (e.g., IL-10 and TGF-β) and the upregulation of immune checkpoint molecules (e.g., PD-L1). Additionally, TAM polarization correlates strongly with prognosis: M2 macrophages are linked to immunosuppression and poor outcomes, while M1 macrophages exhibit antitumor properties. Modulating immune cell proportions and activity in the TME, through immunomodulators or combined chemo-radiotherapy, has demonstrated potential to improve immunotherapeutic outcomes, laying the groundwork for TME-targeted immunotherapy strategies (28).

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy, showing notable success in EC treatment. Anti-PD-1/PD-L1 and anti-CTLA-4 monoclonal antibodies have been particularly effective for patients with MSI-H or dMMR EC (4). However, their efficacy in microsatellite-stable (MSS) EC remains limited due to low T-cell infiltration and elevated expression of immunosuppressive molecules in the TME. To address these challenges, researchers are exploring combination therapies. For example, combining anti-PD-1/PD-L1 antibodies with anti-angiogenic agents like bevacizumab can enhance T-cell infiltration by normalizing the tumor vasculature. Additionally, combining ICIs with chemotherapy, radiotherapy, or targeted therapies is under investigation, aiming to induce immunogenic cell death or bolster antitumor immune responses (35). These approaches offer promising pathways to enhance ICI efficacy in MSS patients.

Chimeric antigen receptor T-cell (CAR-T) therapy is in its nascent stages for EC treatment. Preclinical studies targeting tumor-associated antigens such as MUC1 and HER2 have demonstrated promising anti-improvement activity by adoptive T cell therapy (86, 87). However, clinical application faces challenges such as tumor heterogeneity and immunosuppressive TME (88). To overcome these barriers, researchers are advancing next-generation CAR-T technologies, including dual-specific CAR-T cells targeting multiple antigens and gene-edited CAR-T cells optimized for survival in suppressive environments (39). Combining CAR-T therapy with ICIs or other immunomodulators is also being explored as a potential solution. For example, ICIs block inhibitory signals such as PD-1 and CTLA-4 to prevent T cell exhaustion and enhance anti-tumor effects (35). They reshape the tumor microenvironment, reduce immune suppression, and promote CAR-T cell infiltration and function. Additionally, precise immune regulation helps minimize cytokine release syndrome and other adverse effects, improving safety (38, 79). The synergy of these mechanisms is expected to enhance the efficacy and safety of CAR-T therapy in EC treatment (3, 24).

Epigenetic modifications are increasingly recognized as key players in immune regulation in EC, with methylation and phosphorylation mechanisms being particularly significant. Aberrant DNA methylation can promote immune evasion by silencing immune-related genes, while hyperactive phosphorylation pathways may enhance TME immunosuppression (89). Other epigenetic mechanisms, such as protein acetylation and histone modifications, also warrant further investigation for their roles in tumor immunity (90). Additionally, emerging forms of programmed cell death, such as pyroptosis and cuproptosis, provide new opportunities for inducing tumor immune responses. Pyroptosis, a pro-inflammatory cell death pathway, activates antitumor immunity by releasing immunogenic molecules, while cuproptosis disrupts tumor cell growth through copper ion metabolism regulation (91, 92). Therapeutic strategies leveraging these mechanisms hold potential for significantly enhancing immunotherapy efficacy.

Nanotechnology has also gained attention in immunotherapy applications. Nanoparticles, as drug delivery vehicles, offer advantages in efficient delivery and targeting. For instance, nanoparticles delivering antigens or immunoadjuvants can amplify antitumor immune responses, while CRISPR/Cas9-based nanotechnology enables precise gene editing (93, 94). Nanotechnology-based immunotherapy can also be combined with other treatments, such as photodynamic therapy (PDT) or photothermal therapy (PTT), for improved outcomes (95, 96). Meanwhile, machine learning is emerging as a powerful tool for personalized EC treatment. By integrating multi-omics data (e.g., genomic, transcriptomic, and epigenomic data), machine learning models can predict patient responses to immunotherapy and guide precise drug selection. This combination of big data analytics and artificial intelligence offers a promising avenue for developing more effective, personalized treatment strategies (97, 98).

Overall, EC immunotherapy is advancing toward a multidimensional and integrative paradigm. From dynamic TME regulation and epigenetic exploration to CAR-T therapy optimization and nanotechnology innovation, the field is thriving. However, challenges remain in clinical translation, including treatment safety, efficacy, and cost-effectiveness. Future research should prioritize: (1) Mechanistic Insights: Deepening understanding of immune-tumor interactions within the TME, particularly the immune evasion mechanisms in MSS EC with low immune infiltration. (2) Optimized Combination Therapies: Identifying optimal regimens for ICIs combined with other modalities and expanding clinical trials for low-immune-response patients. (3) Technological Integration: Leveraging machine learning, nanotechnology, and epigenetics to advance precision immunotherapy. (4) Emerging Mechanisms in Practice: Translating novel mechanisms, such as pyroptosis and cuproptosis, into safe and effective clinical strategies.

In conclusion, this bibliometric analysis provides a clear framework to guide future efforts in the pathophysiology, molecular biology, and clinical research of EC immunotherapy. By fostering collaboration and integration across institutions, research teams, and funding bodies, while keeping pace with emerging priorities, EC immunotherapy can advance from foundational research to clinical application, ultimately benefiting a broader patient population.

This study has several limitations that require attention. Firstly, the data source was limited to WoSCC, which, although extensive, may not encompass all relevant publications. Secondly, the quality of the included literature varied considerably, potentially introducing biases and affecting the overall reliability of the analysis results. Moreover, it should be recognized that all bibliometric tools have inherent limitations. During the process of extracting terms from titles, abstracts, and keywords, the results of cluster analysis may fluctuate significantly, and it cannot be fully ensured that terms with similar meanings are accurately consolidated. Although this study enhanced its objectivity and reliability through preregistration and blind design, it is still important to acknowledge that the validity of the research model depends on the selected screening criteria and the quality of the retrieved records. Therefore, future studies should consider integrating multiple databases and standardized tools to gain a more comprehensive and in-depth understanding of global research on EC immunotherapy, thereby forming a more complete and systematic perspective.

As far as we are aware, this study represents a novel comprehensive bibliometric analysis of immunotherapy for EC, offering insights into the current research progress and global trends in this field. The findings reveal that this area is rapidly evolving and is expected to continue expanding in the future. China and the United States are the primary driving forces, holding central positions in global research on this topic. To accelerate progress, future researchers should prioritize fostering greater collaboration across countries and regions. Institutions such as the Texas Medical Anderson Cancer Center and Nanjing Medical University, along with the journal Gynecologic Oncology, have demonstrated exceptional productivity and influence. Research teams led by Bosse, Tjalling, and Creutzberg, Carien L have been pivotal in advancing the field.

Currently, key research hotspots include the “Tumor Immune Microenvironment, “ “Immune Checkpoint Inhibitors,” and “Targeted Therapy.” Looking ahead, promising research directions may focus on further exploring the underlying mechanisms, optimizing combination therapy strategies, and integrating cross-disciplinary technologies to drive the transition of EC immunotherapy strategies from basic research to clinical applications.

In conclusion, this bibliometric analysis provides a comprehensive overview of research in EC immunotherapy, offering valuable insights for researchers and decision-makers while playing a crucial role in guiding the translation of foundational research into practical applications in this field.

The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82160549), the Education Department of Hainan Province (Qhyb2024-185), and Hainan Province Clinical Medical Center.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

YX: Conceptualization, Data curation, Formal Analysis, Methodology, Software, Validation, Visualization, Writing – original draft. TW: Conceptualization, Data curation, Formal Analysis, Methodology, Software, Validation, Visualization, Writing – original draft. XL: Data curation, Software, Validation, Writing – original draft. JY: Data curation, Software, Validation, Writing – original draft. YZ: Data curation, Software, Validation, Writing – original draft. SB: Funding acquisition, Project administration, Resources, Supervision, Validation, Writing – review & editing.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declare that no Generative AI was used in the creation of this manuscript.

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