Immune cell infiltration and cytokine secretion analysis reveal a non-inflammatory microenvironment of medulloblastoma

Medulloblastoma (MB) is the most common lethal malignant pediatric brain tumor. Adjuvant immunotherapy for medulloblastoma has been proposed in both pre-clinical and clinical practice. To provide a precision strategy of designing immunotherapy for MB, the present study performed a descriptive analysis of immune microenvironment in a cohort and compared the differences between four subgroups of MB. Subtypes (WNT, SHH Group 3 and Group 4) of medulloblastoma were identified using K-means clustering according to the expression of signature genes. Tumor infiltrating immune cell population was assessed by both bio-informative algorithm based on gene expression and immunohistochemistry staining. Cytokines in tumor microenvironment were detected using Luminex. Gene Set Enrichment Analysis demonstrated a raised immune response in the SHH subgroup. Lymphocyte infiltration was low in all four subgroups, while more CD4(+) T cells were observed in the Group 4 subtype. Programmed cell death protein 1 (PD1)/ ligand 1 (PD-L1) expression was absent in the cohort. The SHH subtype recruited more activated tumor associated macrophage/microglia compared with the other subgroups. Cytokines within the MB microenvironment were low compared with the glioblastoma samples. In contrast to glioblastoma, the immune microenvironment of pediatric MB is non-inflammatory and does not recruit many immune cells. These observations provide important considerations for the design of immunotherapeutic approaches for MB, such as inducing more lymphocytes into the tumor microenvironment.