Gynecological tumors, including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC), represent a significant global health burden for women. In recent years, both the incidence and mortality rates of these malignancies have exhibited an upward trend, particularly in low- and middle-income countries. CC ranks fourth in terms of both incidence and mortality among female cancers worldwide, with more than 70% of cases occurring in resource-limited settings. Despite the widespread implementation of screening programs, the global survival rate for women with CC has remained stagnant, and the prognosis of metastatic or recurrent disease remains dismal. EC is among the most common gynecologic malignancies in developed countries. Its mortality rate has steadily increased over the past decade, with a 5-year survival rate of only 16% in patients with distant metastases. Ovarian cancer, which is often diagnosed at an advanced stage because of a lack of early symptoms and effective screening tools, remains the most lethal gynecologic cancer. In the United States, it is estimated that approximately 60.9% of newly diagnosed OC cases in 2025 will result in mortality, with a 5-year relative survival rate of only 31% for those with advanced-stage disease. Although standard treatment strategies—comprising surgery and platinum-based chemotherapy—have improved overall outcomes, many patients experience recurrence and progression, highlighting the urgent need for more effective therapeutic approaches. This paper was published in the Chinese Medical Journal on June 17, 2026.
Immunotherapy has emerged as a transformative strategy in cancer treatment, offering durable responses and survival benefits in various malignancies, including non-small cell lung cancer and melanoma. Encouraged by these successes, immunotherapy is being actively explored in the context of gynecologic tumors. Immunotherapeutic modalities such as immune checkpoint inhibitors (ICIs), adoptive cell therapy (ACT), antibody–drug conjugates (ADCs), and oncolytic virus-based vaccines have shown promising clinical potential; these treatments reactivate antitumor immunity and enhance immune recognition by tumor cells.
Among these treatment options, ICIs targeting PD-1/PD-L1 or CTLA-4 have demonstrated notable efficacy, particularly in patients with PD-L1-positive tumors. However, the complex and highly heterogeneous tumor immune microenvironment (TIME) in gynecologic cancers—especially OC—poses a major challenge to immunotherapy success. The TME not only facilitates immune evasion through various mechanisms but also supports tumor growth, angiogenesis, and metastasis via dynamic crosstalk between tumor cells and infiltrating immune cells.
Mounting evidence suggests that the density, phenotype, and functional status of tumor-infiltrating lymphocytes (TILs), particularly cytotoxic CD8⁺ T cells, are closely associated with clinical outcomes and the response to immunotherapy. Nevertheless, tumor cells can impair T-cell activity through multiple immunosuppressive pathways involving regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), inhibitory cytokines, and immune checkpoint molecules. Moreover, the immunological landscape of tumors is influenced by additional factors, such as somatic mutations, abnormal angiogenesis, altered cellular metabolism, and shifts in the tumor-associated microbiome.
Given these complexities, a deeper understanding of the immune landscape in gynecologic tumors and the mechanisms driving immune escape is essential to increasing the efficacy of immunotherapy. This review aims to systematically summarize recent progress in immunotherapy for gynecologic cancers, with a focus on the characteristics of the TME, underlying immune evasion mechanisms, current clinical applications, and emerging therapeutic strategies. We also discuss future directions for precision immunotherapy, aiming to provide a theoretical foundation and practical guidance for optimizing treatment strategies and improving patient prognosis.
Reference
Title of original paper: Immunotherapy for gynecological tumors: From mechanism to clinical practice
Journal: Chinese Medical Journal
DOI: https://doi.org/10.1097/cm9.0000000000004166
About Professor Hui Wang from Zhejiang University
Prof. Hui Wang is the Secretary of the Party Committee of the Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine. She has led over 10 national-level research and development projects, including the National Key Research and Development Program and the National Natural Science Foundation of China. She has published over 40 papers in journals, including Nature Genetics, Journal of Clinical Investigation, Journal of the National Cancer Institute, Drug Resistance Updates, Advanced Science, and Cell Reports Medicine. She has received first prizes at the provincial and ministerial levels and holds four patents, two of which have been converted.
Funding information
This work was supported in part by grants from the programs of Zhejiang Traditional Chinese Medicine Innovation Team (CZ2024009), the National Natural Science Foundation of China (grant 82503123), the Postdoctoral Fellowship Program of CPSF (GZC20241497) and the China Postdoctoral Science Foundation funded project (2024M762860).
