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World J Clin Oncol. Mar 24, 2023; 14(3): 117-130
Published online Mar 24, 2023. doi: 10.5306/wjco.v14.i3.117
Immune microenvironment of medulloblastoma: The association between its molecular subgroups and potential targeted immunotherapeutic receptors
Maher Kurdi, Nasser Mulla, Husam Malibary, Ahmed K Bamaga, Motaz M Fadul, Eyad Faizo, Sahar Hakamy, Saleh Baeesa
Maher Kurdi, Motaz M Fadul, Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh 213733, Saudi Arabia
Maher Kurdi, Neuromuscular Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah 213733, Saudi Arabia
Nasser Mulla, Department of Internal Medicine, Faculty of Medicine, Taibah University, Medina 213733, Saudi Arabia
Husam Malibary, Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 213733, Saudi Arabia
Ahmed K Bamaga, Department of Paediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 213733, Saudi Arabia
Eyad Faizo, Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Tabuk University, Tabuk 213733, Saudi Arabia
Sahar Hakamy, Neurmuscular Unit, Center of Excellence of Genomic Medicine, Jeddah 21423, Saudi Arabia
Saleh Baeesa, Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
Author contributions: All authors shared in writing the review.
Conflict-of-interest statement: All the author declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial [CC BY-NC 4.0] license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maher Kurdi, FRCPC, MD, Associate Professor, Department of Pathology, Faculty of Medicine in Rabigh, King Abdulaziz University, Rabigh 213733, Saudi Arabia. ahkurdi@kau.edu.sa
Received: December 14, 2022
Peer-review started: December 14, 2022
First decision: January 20, 2023
Revised: February 8, 2023
Accepted: February 22, 2023
Article in press: February 22, 2023
Published online: March 24, 2023
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

Keywords: Medulloblastoma, Tumour microenvironment, Tumour associated macrophages, Tumour infiltrating lymphocyte, Immunotherapies

Core Tip: Medulloblastoma (MB) is the most common malignant childhood tumor of the brain. Multimodal treatments consisting of surgery, radiation, and chemotherapy have reduced the cumulative incidence of late mortality. Nevertheless, the recurrence rate remains high. In this review, we discuss the mechanism of interaction between tumour cells of MB and immune cells in the microenvironment, with an overview of the recent investigations and clinical trials.