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 (P = 0.031) and CD4 T cells (P = 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 (P = 0.000) and OS (P = 0.001), while patients without metastasis showed better 5-year PFS (P = 0.031) and OS (P = 0.015). Multivariate analysis showed that CD4 T cells were an independent prognostic factor affecting both the 5-year PFS (P = 0.004, HR = 0.230, 95% CI = 0.085-0.662) and OS (P = 0.017, HR = 0.180, 95% CI = 0.044-0.739). Additionally, it was observed that CD4 T cells exhibited a positive correlation with Mtotal (total macrophages) (P < 0.05, r = 0.249) and Mmix (M1/M2 mixed phenotype macrophages) (P < 0.01, r = 0.325), and CD3+CD8+PD-1+ cells showed a positive correlation with Mmix (P < 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.

Medulloblastoma is one of the most common malignant brain tumors in children, and 75% of patients achieve long-term survival. There are limited studies reporting acute toxicity for pediatric patients receiving proton therapy for craniospinal irradiation (CSI) in medulloblastoma, and these are limited by their retrospective nature, modest cohort sizes, and lack of a comparator group. We analyzed data from the Pediatric Proton/Photon Consortium Registry. Patients with a diagnosis of medulloblastoma, receiving CSI with doses of either 23.4 Gy or 36 to 39.6 Gy, and with toxicity data at baseline and completion of treatment, were identified for inclusion. A total of 272 patients were included for analysis. All patients received proton therapy. The median age of patients was 8 years (range 3-22 years), and 67.6% were male. Most patients were of good performance status with eastern cooperative oncology group (ECOG) 0 or 1, 36.8% and 31.6%, respectively. In total, 68.8% of patients had classic medulloblastoma; 76.8% had M0 disease; and 62.9% of patients had standard-risk disease.Acute toxicities were reported as grade 1 or higher. The most common toxicities occurring during treatment were skin (90.3%), gastrointestinal (71.6%), hematological (54.9%), and mouth (32.0%). Toxicity rates were lower than in the published literature. All patients completed treatment. Our findings suggest that proton CSI has an acceptable degree of acute toxicity in the treatment of pediatric medulloblastoma. Future studies would benefit from toxicity grading, toxicity timing, and a photon comparator group.

Tumor-associated macrophages (TAMs) constitute a significant proportion of the immune cell population within brain tumors. The polarization of macrophages exerts an important influence on the tumor microenvironment (TME). Nevertheless, the specific role of TAMs in sonic hedgehog (SHH) medulloblastoma remains unclear. To investigate the polarization characteristics and effects of TAMs in SHH medulloblastoma, we evaluated the infiltration of M1 and M2 macrophages in SHH medulloblastoma tissues and analyzed the correlation between TAMs recruitment and the clinical outcome of SHH medulloblastoma patients. We enrolled a total of 42 patients diagnosed with SHH medulloblastoma. Using multiple immunofluorescence staining on paraffin-embedded sections, we detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163. Subsequently, we analyzed the correlation between TAMs and clinical characteristics as well as prognostic factors. The median age of 42 patients (31 boys, 11 girls) was 5.3 years (range: 0.8-15.1 years). All patients had confirmed pathological types, including 4 cases of classic medulloblastoma (CMB), 33 cases of desmoplastic/nodular medulloblastoma (DNMB), 3 cases of medulloblastoma with extensive nodularity (MBEN), and 2 cases of large-cell/anaplastic medulloblastoma (LCA). Thirteen cases presented with metastasis at diagnosis, while twenty-nine cases were without metastasis. Four cases had high-risk genetic abnormalities. Different proportions of macrophages were found in the collected medulloblastoma tissues, and large amounts of CD68+HLA-DR+CD163+ cells were found. The study revealed that Mtotal (total macrophages) and Mmix (CD68+HLA-DR+CD163+ cells) were significantly higher in group of patients <5 years old (P < 0.05), and Mtotal in non-metastatic group were significantly higher than that in metastatic group (P = 0.043). M2 macrophages in CMB group were significantly higher than that in DNMB/MBEN group (P = 0.036), M1 macrophages were significantly higher in children without high-risk genetic abnormalities (P = 0.007). Five-year PFS was significantly poorer in patients ≥5 years old and metastatic group (P < 0.05). High Mtotal group had a better 5-year PFS (P = 0.000), whereas high M2 group had both better 5-year PFS and OS (P = 0.001, P = 0.001). Multivariate analysis showed that Mtotal and M2 macrophages were independent prognostic factors for 5-year PFS, and M2 macrophages were an independent prognostic factor for 5-year OS. The increase in total macrophages and M2 macrophages predicts a better outcome of SHH medulloblastoma. TAMs especially M2 macrophages might be a therapeutic target for SHH medulloblastoma.

Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.

Medulloblastoma (MB) is a rapidly growing malignant solid tumor that arises from stem cells located in the subependymal germinal matrix or outer granular layer of the cerebellum. It represents 15 to 30% of pediatric brain tumors and less than 1% of primary brain tumors. The reason for the high incidence of MB in children compared to adults is the embryonic origin of the tumor. In typical cases, MB manifests as a solitary lesion in the fourth ventricle or in the cerebellar parenchyma; cases of synchronous multifocal and disseminated MB are quite rare in patients without familial tumor syndromes. To date, only 7 cases in adults and a single pediatric case with Gorlin syndrome have been described previously. Here, the authors report a new case of synchronous multifocal classic cerebrospinal histologically confirmed MB in a 10-year-old male patient revealed by bilateral decreased visual acuity without any other localizing neurological signs. The authors will proceed with a review of the current literature regarding this rare entity.