Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy.

in Current neuropharmacology by Sarasa Meenakshi, Krushna Ch Maharana, Lokesh Nama, V Udaya Kumar, Sameer Dhingra, Velayutham Ravichandiran, Krishna Murti, Nitesh Kumar

TLDR

  • The study is about finding new ways to treat brain tumors in kids. They looked at how certain proteins and changes in the proteins in the brain can help the tumors grow. They found that there are certain changes that happen in the proteins that can help the tumors grow. They also found that there are certain proteins that can help stop the tumors from growing. They think that using these proteins and changes in the proteins could help make better treatments for brain tumors in kids.

Abstract

Despite little progress in survival rates with regular therapies, which do not provide complete care for curing pediatric brain tumors (PBTs), there is an urgent need for novel strategies to overcome the toxic effects of conventional therapies to treat PBTs. The co-inhibitory immune checkpoint molecules, e.g., CTLA-4, PD-1/PD-L1, etc., and epigenetic alterations in histone variants, e.g., H3K27me3 that help in immune evasion at tumor microenvironment have not gained much attention in PBTs treatment. However, key epigenetic mechanistic alterations, such as acetylation, methylation, phosphorylation, sumoylation, poly (ADP)-ribosylation, and ubiquitination in histone protein, are greatly acknowledged. The crucial checkpoints in pediatric brain tumors are cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PDL1), OX-2 membrane glycoprotein (CD200), and indoleamine 2,3-dioxygenase (IDO). This review covers the state of knowledge on the role of multiple co-inhibitory immunological checkpoint proteins and histone epigenetic alterations in different cancers. We further discuss the processes behind these checkpoints, cell signalling, the current scenario of clinical and preclinical research and potential futuristic opportunities for immunotherapies in the treatment of pediatric brain tumors. Conclusively, this article further discusses the possibilities of these interventions to be used for better therapy options.

Overview

  • The study aims to explore the role of co-inhibitory immune checkpoint molecules and histone epigenetic alterations in pediatric brain tumors (PBTs).
  • The methodology used for the experiment includes a review of the literature on the topic, with a focus on clinical and preclinical research.

Comparative Analysis & Findings

  • The study identifies key epigenetic mechanistic alterations, such as acetylation, methylation, phosphorylation, sumoylation, poly (ADP)-ribosylation, and ubiquitination in histone protein, as crucial checkpoints in pediatric brain tumors.

Implications and Future Directions

  • The study highlights the potential of immunotherapies to be used for better therapy options in the treatment of pediatric brain tumors. Future research should focus on developing novel strategies to overcome the toxic effects of conventional therapies and target these key epigenetic mechanistic alterations.
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