Background. Classical Hodgkin’s lymphoma (cHL) in adolescents between 15 and 18 years old shows a higher disease-related mortality, and the overall prognosis is worse than in both children and adults. Objectives. We investigated the immune checkpoint inhibitors (ICPIs) therapeutic targets and specific T-regulatory and cytotoxic T-cell subsets in the subgroup of adolescent cHL patients, and we challenged their prognostic power. Methods. We retrieved formalin-fixed paraffin-embedded (FFPE) tissue of adolescent patients diagnosed with cHL and tested by immunohistochemistry the immune checkpoint molecules CTLA-4, LAG-3, PD-1, and PDL1 as well as the biological markers FOXP3 and CD8. Results. All the cases of our cohort expressed the immune checkpoint molecules CTLA-4, LAG-3, and PD-1 in microenvironment (ME), and the number of PD1+ cells was strongly associated with advanced disease, being higher in stage III/IV, indicating a possible role in the progression of cHL. A higher risk of recurrence and progression occurred in patients with lower amount of CD8+ microenvironmental T-cells at diagnosis (67.14 ± 27.23 vs. 42.86 ± 17.33p= 0.032 and 65.59 ± 26.68 vs. 37 ± 17.45p =0.046, respectively). Conclusions. We showed that microenvironment of cHL in adolescent patients is enriched with potential therapeutic targets of ICPI that may be considered for therapeutic applications. Furthermore, the presence of PD-1 expressing T-cells strongly relates to advanced stage disease and a low density of CD8+ T lymphocytes is associated with recurrence and progression of disease.
背景：15至18岁青少年经典霍奇金淋巴瘤（cHL）的疾病相关死亡率较高，总体预后较儿童及成人患者更差。目的：本研究旨在探讨青少年cHL患者亚群中免疫检查点抑制剂（ICPI）的治疗靶点及特异性调节性T细胞与细胞毒性T细胞亚群，并评估其预后预测价值。方法：收集经福尔马林固定石蜡包埋（FFPE）的青少年cHL患者组织样本，采用免疫组织化学法检测免疫检查点分子CTLA-4、LAG-3、PD-1、PD-L1及生物标志物FOXP3、CD8的表达情况。结果：本队列所有病例的肿瘤微环境（ME）均表达CTLA-4、LAG-3和PD-1免疫检查点分子，其中PD1+细胞数量与疾病晚期显著相关（III/IV期患者表达量更高），提示其可能在cHL进展中发挥作用。诊断时CD8+微环境T细胞数量较低的患者复发与进展风险更高（分别为67.14±27.23 vs. 42.86±17.33，p=0.032；65.59±26.68 vs. 37±17.45，p=0.046）。结论：青少年cHL患者的肿瘤微环境中富含ICPI潜在治疗靶点，具有临床转化价值。此外，PD-1阳性T细胞的存在与疾病晚期密切相关，而CD8+T淋巴细胞密度降低与疾病复发及进展相关。
Microenvironmental Traits of Classical Hodgkin’s Lymphoma in Adolescents and Their Prognostic Impact
肿瘤(癌症)患者之家