DECIPHERING THE IMMUNE LANDSCAPE OF OVARIAN CANCER: AN IN-DEPTH ANALYSIS OF IGCH CD4+, CD8+, AND PD-L1 IN TUMOR MICROENVIRONMENT AND THEIR THERAPEUTIC IMPLICATIONS
Abstract
Relevance. Ovarian cancer is one of the most lethal gynecological malignancies worldwide, with high mortality primarily due to late-stage diagnosis and the lack of effective early screening. The tumor microenvironment (TME) plays a crucial role in cancer progression, immune evasion, and resistance to therapy. Immune cells, particularly CD4+ and CD8+ T cells, along with immune checkpoint proteins like PD-L1, significantly influence tumor behavior and therapeutic response. Understanding their roles in ovarian cancer may provide insights into novel immunotherapeutic strategies. Materials and methods of study. A total of 135 ovarian cancer patients from the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology, Samarkand Branch, were included in this study. Tumor samples were obtained through biopsy or surgical resection, and immune profiling was performed using multiplex immunohistochemistry and flow cytometry. The expression levels of CD4+, CD8+, and PD-L1 were quantified, and their spatial distribution within the TME was analyzed. Correlations between immune profiles and clinical outcomes, including survival rates and response to immunotherapy, were assessed. Research results. CD4+ T helper cells exhibited functional diversity, with Th1 cells promoting anti-tumor immunity, whereas Th2 and regulatory T cells (Tregs) contributed to immune suppression in advanced tumors. High CD8+ T-cell infiltration correlated with improved survival; however, elevated PD-L1 expression was associated with T-cell exhaustion (PD-1, TIM-3, LAG-3) and immune evasion. Increased PD-L1 levels were linked to poor prognosis, reinforcing its role as a key immune checkpoint regulator. Conclusion. This study highlights the prognostic significance of CD4+, CD8+, and PD-L1 expression in ovarian cancer. Immune profiling may aid in personalized treatment strategies, optimizing immunotherapy efficacy. Future research should focus on integrating multi-omics approaches to enhance patient stratification and improve therapeutic outcomes.
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List of references
Wang, Y., Zhou, Y., Yang, L., et al. (2024). Spatial heterogeneity expression of PD‐L1 in cancer therapy. Advanced Science, 11(1), 2303175.
Lotze, M. T., Olejniczak, S. H., & Skokos, D. (2024). CD28 co-stimulation: Novel insights in cancer immunotherapy. Nature Reviews Immunology.
Ren, X., Wang, L., Liu, L., et al. (2024). PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy. Frontiers in Immunology, 15, 1392546.
Mima, Y., Ohtsuka, T., Ebato, I., et al. (2024). T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment. Biomedicines, 12(8), 1886.
Ni, R., Hu, Z., & Tao, R. (2024). Advances of immune-checkpoint inhibition of CTLA-4 in pancreatic cancer. Biomedicine & Pharmacotherapy, 179, 117430.
Johnson, D. B., Estrada, M. V., Salgado, R., et al. (2024). Immune profiling in gynecologic cancers: a biomarker approach. Journal of Clinical Oncology, 42(3), 204-215.
Miller, A. M., Lundberg, I. V., Ozbek, U., et al. (2024). Tumor-infiltrating lymphocytes in ovarian cancer: their prognostic role and therapeutic implications. Cancer Immunology Research, 12(5), 765-780.
Nakamura, K., Smyth, M. J., & Martinet, L. (2024). Role of natural killer cells in ovarian cancer and the impact of checkpoint blockade therapy. Nature Cancer Reviews, 5(2), 142-156.
White, E. E., Rhodes, S. D., et al. (2024). The NF1+/-Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation. Cancers, 16(5), 994.
Lawton, M. L., Inge, M. M., Blum, B. C., et al. (2024). Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming. PLoS Biology, 22(12), e3002943.
Hashemi, M., Khosroshahi, E. M., Daneii, P., et al. (2024). Emerging roles of CircRNA-miRNA networks in cancer development and therapeutic response. Non-coding RNA Research.
Wang, X., Yang, M., Zhu, J., et al. (2024). Role of exosomal non coding RNAs in ovarian cancer. International Journal of Molecular Medicine, 54(4), 87.
Elemam, N. M., Mekky, R. Y., Rashid, G., et al. (2024). Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology. Expert Reviews in Molecular Medicine, 26, e1.