Asare-Werehene Meshach, Zaker Arvin, Tripathi Shivanshi, Communal Laudine, Carmona Euridice, Mes-Masson Anne-Marie, Tsang Benjamin K, Mer Arvind
Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, ON, Canada.
Department of Cellular and Molecular Medicine & The Centre for Infection, Immunity and Inflammation (CI3), Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Front Immunol. 2025 Jul 14;16:1543529. doi: 10.3389/fimmu.2025.1543529. eCollection 2025.
Ovarian cancer (OVCA) has a five-year survival rate of approximately 45%, with little improvement over recent decades. Although anti-PD-L1 therapies have shown substantial efficacy in other solid tumors, their effectiveness in OVCA has been limited. These treatments target only membranous and soluble forms of PD-L1, without addressing nuclear-localized PD-L1. The role of nuclear PD-L1 in OVCA chemoresistance, however, remains largely unexplored. In this study, we examined the prognostic significance of nuclear PD-L1 and its interactions with plasma gelsolin (pGSN) and CD8+ T cells within the tumor microenvironment.
Using immunofluorescence, we quantified nuclear PD-L1, pGSN, and additional markers in OVCA samples. Statistical analyses and machine learning approaches were employed to assess associations between marker expression, patient outcomes, and chemoresistance.
Increased nuclear PD-L1 was associated with disease recurrence, chemoresistance and poor overall survival. Although CD8+ T cells provided survival benefits to patients, elevated PD-L1 hindered these benefits resulting in shortened disease free (DFS) and overall survival (OS). Co-expression of PD-L1 and pGSN was also associated with shortened DFS, OS and chemoresistance.
These findings indicate that nuclear PD-L1 serves as a poor prognostic marker in OVCA, being associated with tumor recurrence, chemoresistance, and reduced overall survival. Targeting nuclear PD-L1 may represent a novel therapeutic strategy to improve outcomes in patients with OVCA.
卵巢癌（OVCA）的五年生存率约为45%，近几十年来几乎没有改善。尽管抗PD-L1疗法在其他实体瘤中已显示出显著疗效，但其在卵巢癌中的有效性有限。这些治疗仅针对膜结合型和可溶性PD-L1形式，而未涉及核定位的PD-L1。然而，核PD-L1在卵巢癌化疗耐药中的作用在很大程度上仍未得到探索。在本研究中，我们研究了核PD-L1的预后意义及其与肿瘤微环境中血浆凝溶胶蛋白（pGSN）和CD8 + T细胞的相互作用。
我们使用免疫荧光法对卵巢癌样本中的核PD-L1、pGSN和其他标志物进行定量。采用统计分析和机器学习方法评估标志物表达、患者预后和化疗耐药之间的关联。
核PD-L1水平升高与疾病复发、化疗耐药和总体生存率低相关。尽管CD8 + T细胞为患者提供了生存益处，但升高的PD-L1阻碍了这些益处，导致无病生存期（DFS）和总生存期（OS）缩短。PD-L1和pGSN的共表达也与DFS、OS缩短和化疗耐药相关。
这些发现表明，核PD-L1是卵巢癌预后不良的标志物，与肿瘤复发、化疗耐药和总生存期降低相关。靶向核PD-L1可能代表一种改善卵巢癌患者预后的新治疗策略。
