Immune microenvironment of medulloblastoma: The association between its molecular subgroups and potential targeted immunotherapeutic receptors.

Abstract

Medulloblastoma (MB) is considered the commonest malignant brain tumor in children. Multimodal treatments consisting of surgery, radiation, and chemotherapy have improved patients' survival. Nevertheless, the recurrence occurs in 30% of cases. The persistent mortality rates, the failure of current therapies to extend life expectancy, and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches. Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections. Recently, MBs have been segregated into four molecular subgroups: Wingless-activated (WNT-MB) (Group 1); Sonic-hedgehog-activated (SHH-MB) (Group 2); Group 3 and 4 MBs. These molecular alterations follow specific gene mutations and disease-risk stratifications. The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival. However, the need to explore new therapies targeting specific receptors in MB microenvironment became essential. The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells. Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment, and their role are still under investigation. In this review, we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment, with an overview of the recent investigations and clinical trials.