Bone Marrow Transplantation Center, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
Int J Cancer. 2012 Sep 1;131(5):1142-52. doi: 10.1002/ijc.27314. Epub 2011 Dec 21.
Classical Hodgkin lymphoma (cHL) is characterized by a small number of neoplastic cells in a background of reactive cells. Children and adults differ in constitution and functionality of the immune system and it is possible that there may be age-related differences in tumor microenvironment composition in cHL. One hundred children with pediatric cHL were studied. Tumor-infiltrating lymphocytes were analyzed by immunohistochemistry (IHC) and image analysis. Epstein-Barr virus (EBV) status was determined by EBER-specific in situ hybridization and IHC. Results were analyzed in the context of age-group, histological characteristics and clinical follow-up. EBV-status was not associated with age-group. Children<10 years and EBV+ cases were characterized by a more intense T cell infiltrate, exhibiting a cytotoxic/Th1 profile, characterized by higher numbers of CD3+, CD8+, TIA1+ and TBET+ lymphocytes. Extranodal disease (p=0.016) and high number of GranzymeB+ lymphocytes (p=0.04) were independently associated with reduced progression-free survival (PFS). Yet, in EBV+ cases, improved outcome was observed in cases with low numbers of FOXP3+ lymphocytes (p=0.046), FOXP3/CD8 ratio<1 (p=0.021) and TBET/CMAF ratio<1 (p=0.017). By contrast, in EBV- cases, poor survival was observed in cases with extranodal disease (p=0.028), MC subtype (p=0.009) and high numbers of TIA1+ (p=0.044) and GranzymeB+ (p=0.04) lymphocytes. The results suggest that in EBV+ cHL an effective immune response directed against viral or tumor antigens may be triggered in the tumor microenvironment and that physiological and age-related changes of the immune system may also modulate the tumor microenvironment in pediatric cHL.
经典型霍奇金淋巴瘤（cHL）的特征是在反应性细胞背景下存在少量肿瘤细胞。儿童和成人在免疫系统的构成和功能上存在差异，因此在 cHL 肿瘤微环境组成方面可能存在与年龄相关的差异。研究了 100 例儿科 cHL 患儿。通过免疫组织化学（IHC）和图像分析分析肿瘤浸润淋巴细胞。通过 EBER 特异性原位杂交和 IHC 确定 EBV 状态。根据年龄组、组织学特征和临床随访结果分析结果。EBV 状态与年龄组无关。<10 岁的儿童和 EBV+病例的 T 细胞浸润更强烈，表现出细胞毒性/Th1 表型，CD3+、CD8+、TIA1+和 TBET+淋巴细胞数量较高。结外疾病（p=0.016）和高数量的 GranzymeB+淋巴细胞（p=0.04）与无进展生存期（PFS）降低独立相关。然而，在 EBV+病例中，FOXP3+淋巴细胞数量低（p=0.046）、FOXP3/CD8 比值<1（p=0.021）和 TBET/CMAF 比值<1（p=0.017）的病例观察到改善的结果。相比之下，在 EBV-病例中，结外疾病（p=0.028）、MC 亚型（p=0.009）、TIA1+（p=0.044）和 GranzymeB+（p=0.04）淋巴细胞数量高的病例预后较差。结果表明，在 EBV+ cHL 中，针对病毒或肿瘤抗原的有效免疫反应可能在肿瘤微环境中被触发，并且免疫系统的生理和年龄相关变化也可能调节儿科 cHL 中的肿瘤微环境。
