The Growing Relevance of Immunoregulation in Pediatric Brain Tumors

Abstract

Pediatric brain tumors are genetically heterogeneous solid neoplasms. With a prevailing poor prognosis and widespread resistance to conventional multimodal therapy, these aggressive tumors are the leading cause of childhood cancer-related deaths worldwide. Advancement in molecular research revealed their unique genetic and epigenetic characteristics and paved the way for more defined prognostication and targeted therapeutic approaches. Furthermore, uncovering the intratumoral metrics on a single-cell level placed non-malignant cell populations such as innate immune cells into the context of tumor manifestation and progression. Targeting immune cells in pediatric brain tumors entails unique challenges but promising opportunities to improve outcome. Herein, we outline the current understanding of the role of the immune regulation in pediatric brain tumors.

Multi‐institution analysis of tumor mutational burden and outcomes in pediatric central nervous system tumor patients

“…These responses have been demonstrated in non‐small cell lung cancer, malignant melanoma, cervical cancer, breast cancer, gastric, esophageal, and head and neck cancers 19,20,23–25 . In pediatrics, however, responses have been inconsistent, possibly because of the relatively low TMB of pediatric cancers 26,27 …”

Multi-institution analysis of tumor mutational burden and outcomes in pediatric CNS tumor patients

“…18,19,[22][23][24] In pediatrics, however, responses have been inconsistent, possibly because of the relatively low TMB of pediatric cancers. 25,26 There are over 2,000 clinical trials investigating ICI in patients of all ages and with all tumor types (accessed June 2022). Of the 141 trials investigating ICI in pediatric patients, five of which have or are currently investigating ICI in pediatric CNS tumor patients.…”

Three-Dimensional Cell Culture Systems in Pediatric and Adult Brain Tumor Precision Medicine

“…In recent years, several groups have started elucidating the essential role of the TME in brain tumor progression, immune escape, and chemoresistance [ 11 , 12 , 49 , 50 , 51 ]. Therefore, in vitro models should ideally recapitulate the rich gamut of cells, extracellular matrix, and signaling of the TME.…”

“…Importantly, heterogeneous in vivo-like tumor cell populations respond differently to drug treatment than 2D in vitro entities, and intratumoral diversity results in a higher risk of treatment resistance and tumor recurrence [ 9 , 10 ]. Furthermore, the interplay of tumor cells with their TME, including endothelial cells, immune cells, and neuronal cells, affects the treatment response [ 11 , 12 ]. Therefore, it has become paramount to establish models which include these key characteristics and allow tumor–TME interactions, thus potentially generating more accurate predictions of tumor biology, drug efficacy, and immune response.…”