Zhang Jin, Ren Siqi, Li Shuting, Wang Yuan, Wan Lulu, Gao Wenchao, Sun Huaying, Gong Xiaojun, Li Miao, Sun Yanling, Sun Liming, Li Zhigang, Wang Tianyou, Du Shuxu, Wu Wanshui
Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Oncol. 2025 Jun 12;15:1593329. doi: 10.3389/fonc.2025.1593329. eCollection 2025.
T cells and tumor-associated macrophages (TAMs) are critical immune components within the brain tumor microenvironment (TME), yet their precise roles in medulloblastoma remains unclear. In this study, we examined the infiltration characteristics of T cells in medulloblastoma tissues and analyzed the correlation between T cells and the clinical outcomes of medulloblastoma patients. Additionally, we further investigated the relationship between T cells and TAMs.
We enrolled a total of 72 patients diagnosed with medulloblastoma and subsequently detected the T cell makers and programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) in paraffin-embedded sections using multiple immunofluorescence staining method. The correlation between T cell infiltration, clinical characteristics and prognosis were analyzed. Finally, we used Spearman correlation analysis to evaluate the correlation between T cells and TAMs.
The median age at diagnosis of 72 patients (54 boys, 18 girls) was 7.5 years (range: 0.8-18 years). These patients included 43 cases of classic medulloblastoma (CMB), 24 cases of desmoplastic/nodular medulloblastoma (DNMB), 2 cases of medulloblastoma with extensive nodularity (MBEN) and 3 cases of large-cell/anaplastic medulloblastoma (LCA). The molecular subgroups consisted of 3 wingless (WNT), 29 sonic hedgehog (SHH) and 40 non-WNT/non-SHH cases. Twenty-five cases presented with metastasis at diagnosis, while 47 cases were without metastasis. Thirteen cases exhibited with high-risk genetic abnormalities. The total T cells ( = 0.031) and CD4 T cells ( = 0.045) were significantly elevated in the SHH subgroup compared to those in the non-WNT/non-SHH subgroup. Patients with increased CD4 T cells had better 5-year PFS ( = 0.000) and OS ( = 0.001), while patients without metastasis showed better 5-year PFS ( = 0.031) and OS ( = 0.015). Multivariate analysis showed that CD4 T cells were an independent prognostic factor affecting both the 5-year PFS ( = 0.004, HR = 0.230, 95% CI = 0.085-0.662) and OS ( = 0.017, HR = 0.180, 95% CI = 0.044-0.739). Additionally, it was observed that CD4 T cells exhibited a positive correlation with M (total macrophages) ( < 0.05, r = 0.249) and M (M1/M2 mixed phenotype macrophages) ( < 0.01, r = 0.325), and CD3CD8PD-1 cells showed a positive correlation with M ( < 0.05, r = 0.258).
The increase in CD4 T cells predicts a better prognosis in medulloblastoma patients, particularly within the SHH and non-WNT/non-SHH subgroups, and they may serve as a potential therapeutic target for medulloblastoma. Additionally, there may be a potential interaction between CD4 T cells and TAMs that warrants further investigation.
T细胞和肿瘤相关巨噬细胞（TAM）是脑肿瘤微环境（TME）中的关键免疫成分，但其在髓母细胞瘤中的精确作用仍不清楚。在本研究中，我们检测了髓母细胞瘤组织中T细胞的浸润特征，并分析了T细胞与髓母细胞瘤患者临床结局之间的相关性。此外，我们进一步研究了T细胞与TAM之间的关系。
我们共纳入72例诊断为髓母细胞瘤的患者，随后采用多重免疫荧光染色法检测石蜡包埋切片中的T细胞标志物以及程序性死亡1/程序性死亡配体1（PD-1/PD-L1）。分析T细胞浸润、临床特征与预后之间的相关性。最后，我们使用Spearman相关性分析来评估T细胞与TAM之间的相关性。
72例患者（54例男孩，18例女孩）的诊断时中位年龄为7.5岁（范围：0.8 - 18岁）。这些患者包括43例经典型髓母细胞瘤（CMB）、24例促纤维增生性/结节型髓母细胞瘤（DNMB）、2例广泛结节型髓母细胞瘤（MBEN）和3例大细胞/间变型髓母细胞瘤（LCA）。分子亚组包括3例翼状胬肉（WNT）、29例音猬因子（SHH）和40例非WNT/非SHH病例。25例患者诊断时出现转移，47例无转移。13例表现出高危基因异常。与非WNT/非SHH亚组相比，SHH亚组中的总T细胞（P = 0.031）和CD4 T细胞（P = 0.045）显著升高。CD4 T细胞增加的患者5年无进展生存期（PFS）（P = 0.000）和总生存期（OS）（P = 0.001）更好，而无转移的患者5年PFS（P = 0.031）和OS（P = 0.015）更好。多因素分析显示，CD4 T细胞是影响5年PFS（P = 0.004，HR = 0.230，95%CI = 0.085 - 0.662）和OS（P = 0.017，HR = 0.180，95%CI = 0.044 - 0.739）的独立预后因素。此外，观察到CD4 T细胞与M（总巨噬细胞）呈正相关（P < 0.05，r = 0.249）和M（M1/M2混合表型巨噬细胞）呈正相关（P < 0.01，r = 0.325），且CD3CD8PD-1细胞与M呈正相关（P < 0.05，r = 0.258）。
CD4 T细胞增加预示着髓母细胞瘤患者预后较好，尤其是在SHH和非WNT/非SHH亚组中，它们可能作为髓母细胞瘤的潜在治疗靶点。此外，CD4 T细胞与TAM之间可能存在潜在相互作用，值得进一步研究。
