Pediatric glioblastoma: mechanisms of immune evasion and potential therapeutic opportunities

Abstract

Pediatric glioblastoma is relatively rare compared with its adult counterpart but is associated with a similarly grim prognosis. Available data indicate that pediatric glioblastomas are molecularly distinct from adult tumors, and relatively little is known about the pediatric glioblastoma tumor microenvironment (TME). Cancer immunotherapy has emerged as a new pillar of cancer treatment and is revolutionizing the care of patients with many advanced solid tumors, including melanoma, non-small cell lung cancer, head and neck cancer, and renal cell carcinoma. Unfortunately, attempts to treat adult glioblastoma with current immunotherapies have had limited success to date. Nevertheless, the immune milieu in pediatric glioblastoma is distinct from that found in adult tumors, and evidence suggests that pediatric tumors are less immunosuppressive. As a result, immunotherapies should be specifically evaluated in the pediatric context. The purpose of this review is to explore known and emerging mechanisms of immune evasion in pediatric glioblastoma and highlight potential opportunities for implementing immunotherapy in the treatment of these devastating pediatric brain tumors.

Keywords: Cancer immunotherapy; Immune evasion; Immune suppression; Immune system; Pediatric glioblastoma.

Fig. 1

Immune altering mechanisms in pediatric glioblastoma. Created with BioRender.com CD80, cluster of differentiation 80; CD86, cluster of differentiation 86; CD94, cluster of differentiation 94; CSC, cancer stem cell; CTL, cytotoxic T lymphocyte; DC, dendritic cells; HIF-1, hypoxic inducible factor 1; HLA, human leucocyte antigen; IDO1, indolamine 2,3 dioxygenase 1; IL-6, interleukin 6; IL-10, interleukin 10; LDH5, lactate dehydrogenase 5; MICB, MHC class I related gene B; MIF, macrophage migration inhibitory factor; miR, microRNA; MMP9, matrix metalloproteinase-9; PD-1, programmed cell death protein 1; PDL-1, programmed death ligand 1; p-GBM; pediatric glioblastoma; PlGF, placental growth factor; S1P1, sphingosine 1 phosphate; S1P1R, sphingosine 1 phosphate receptor; STAT-3, signal transducer activator of transcription-3; TCR, T cell receptor; TDO, tryptophan dioxygenase; TLR, toll-like receptor; Tregs, regulatory T cells