Department of Immuno-Histo-Cytology, Salah Azaiez Institute, 1006 Tunis, Tunisia; Department of Biology, Mycology, Pathologies, and Biomarkers Laboratory (LR16ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, 2092 Ariana, Tunisia.
Department of Immuno-Histo-Cytology, Salah Azaiez Institute, 1006 Tunis, Tunisia; Department of Biology, Mycology, Pathologies, and Biomarkers Laboratory (LR16ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, 2092 Ariana, Tunisia.
Hum Immunol. 2022 Dec;83(12):843-856. doi: 10.1016/j.humimm.2022.08.013. Epub 2022 Sep 6.
Classical Hodgkin lymphoma (CHL) is characterized by extensive inflammatory immune cells, which predict the disease prognosis. Therefore, this study aimed to explore the significance of different tumor-infiltrated immune cells and subpopulation ratios observed in the tumor microenvironment of CHL, particularly relating to the disease's prognosis-focusing on overall survival (OS) and event-free survival (EFS). Utilizing immunohistochemistry, the quantification and exploration of selected immune cells' subsets, including CD3+, CD4+, CD8+, FOXP3+, CD20+, and CD68+ were conducted on 102 histological samples with primary CHL. Eosinophils were pathologically assessed. Besides, we determined the ratios between different tumor-infiltrated immune cells for each patient. Kaplan-Meier method and Cox regression modeling were used for survival analysis. We demonstrated that among all ratios and immune cells individually, only a higher FOXP3+/CD68+ ratio (≥1.36 cutoff) displayed a tendency towards a favorable OS (p = 0.057, HR = 0.43 [0.18-1.02]) and EFS (p = 0.067, HR = 0.44 [0.18-1.06]) using Cox regression modeling. Moreover, the Kaplan-Meier method showed an association of a higher FOXP3+/CD68+ ratio with a longer 5-years OS (p = 0.037) and a tendency to a better EFS (p = 0.051); however, neither the combined FOXP3+ and CD68+ nor FOXP3+ or CD68+ separately was correlated to the CHL survival. Together, these results demonstrated that the FOXP3+/CD68+ ratio could predict the outcomes of CHL, providing more informative significance than FOXP3+ and CD68+ combined or FOXP3+ and CD68+ individually and might be a potential indicator of risk stratification, which has an important value for guiding the clinical treatment.
经典霍奇金淋巴瘤（CHL）的特征是广泛存在炎症免疫细胞，这些细胞可以预测疾病的预后。因此，本研究旨在探索 CHL 肿瘤微环境中不同浸润免疫细胞亚群比例的意义，特别是与疾病的总生存（OS）和无事件生存（EFS）相关的意义。本研究采用免疫组化方法，对 102 例原发性 CHL 组织学样本进行了 CD3+、CD4+、CD8+、FOXP3+、CD20+和 CD68+等选定免疫细胞亚群的定量和分析。同时对嗜酸性粒细胞进行了病理评估。此外，我们还确定了每位患者不同肿瘤浸润免疫细胞之间的比例。采用 Kaplan-Meier 方法和 Cox 回归模型进行生存分析。结果表明，在所有比值和免疫细胞中，只有更高的 FOXP3+/CD68+比值（≥1.36 截值）与 OS（p=0.057，HR=0.43 [0.18-1.02]）和 EFS（p=0.067，HR=0.44 [0.18-1.06]）的改善趋势相关。此外，Kaplan-Meier 方法表明，更高的 FOXP3+/CD68+比值与更长的 5 年 OS 相关（p=0.037），并与更好的 EFS 趋势相关（p=0.051）；然而，FOXP3+和 CD68+的联合或 FOXP3+和 CD68+的单独表达均与 CHL 生存无关。综上所述，这些结果表明，FOXP3+/CD68+比值可以预测 CHL 的预后，比 FOXP3+和 CD68+的联合或 FOXP3+和 CD68+的单独表达提供了更有意义的信息，可能是风险分层的潜在指标，对指导临床治疗具有重要价值。
