Exhausted and Senescent CD4+ T Cells in Peripheral Blood and Their Impact as a Biological Marker for the Diagnosis of Benign and Malignant Ovarian Tumors

<b>Introduction:</b> Serum biomarkers such as CA-125 and HE4, along with the ROMA score, (which integrates both markers) are widely used to distinguish between benign and malignant ovarian tumors. In ovarian cancer, chronic exposure to tumor-associated antigens (TAAs), such as CA-125 and HE4, can lead to T cell exhaustion and senescence, thereby facilitating immune evasion. This study aimed to evaluate exhausted and senescent T cells in the peripheral blood of patients with benign or malignant ovarian tumors, and compare these findings to those of healthy donors, and assess their correlation with the ROMA score. <b>Methods:</b> The expression of senescent and exhaustion markers was evaluated on peripheral CD4⁺ T cells from patients with benign and malignant ovarian tumors, as well as healthy donors. Multicolor flow cytometry was performed to evaluate the expression of CTLA-4, PD-1, Tim3, CD28, CD57, and CD27. <b>Results:</b> PD1⁺Tim3⁺CD4⁺ expression was significantly higher in the malignant group compared to both the benign group (<i>p</i> = 0.05) and healthy donors (<i>p</i> = 0.015). A positive and significant correlation was observed between ROMA and PD-1⁺Tim3⁺ T cells (r = 0.44, <i>p =</i> 0.0006). The confusion matrix demonstrated good classification accuracy, and in the ROC analysis, the combination of ROMA and PD-1⁺Tim3⁺ yielded the highest Youden Index (0.75) and superior specificity (88.8%) compared to ROMA alone, albeit with a slight reduction in sensitivity (86.9% vs. 91.3%). A nomogram integrating ROMA and PD-1⁺Tim3⁺ exhibited strong predictive performance, with a concordance index (C-index) of 0.91. <b>Conclusion:</b> The combination of the ROMA score with the expression of PD-1⁺ and Tim-3⁺ in CD4⁺ T cells creates a simple yet highly effective model to differentiate between benign and malignant ovarian tumors.