Spatial analysis of a complete DIPG-infiltrated brainstem reveals novel ligand-receptor mediators of tumour-to-TME crosstalk.

in Acta neuropathologica communications by Anja Kordowski, Onkar Mulay, Xiao Tan, Tuan Vo, Ulrich Baumgartner, Mellissa K Maybury, Timothy Hassall, Lachlan Harris, Quan Nguyen, Bryan W Day

TLDR

  • The study identified novel interactions between DIPG tumour cells and the TME, highlighting potential therapeutic targets for treatment.
  • These interactions involve the complements component system and the neuropeptide/GPCR ligand-receptor pair ADCYAP1-ADCYAP1R1.
  • These findings could improve our understanding of disease progression and lead to improved therapeutic strategies for DIPG treatment.

Abstract

Previous studies have highlighted the capacity of brain cancer cells to functionally interact with the tumour microenvironment (TME). This TME-cancer crosstalk crucially contributes to tumour cell invasion and disease progression. In this study, we performed spatial transcriptomic sequencing analysis of a complete annotated tumour-infiltrated brainstem from a single diffuse intrinsic pontine glioma (DIPG) patient. Gene signatures from ten sequential tumour regions were analysed to assess mechanisms of disease progression and oncogenic interactions with the TME. We identified four distinct tumour subpopulations and assessed respective ligand-receptor pairs that actively promote DIPG tumour progression via crosstalk with endothelial, neuronal and immune cell communities. Our analysis found potential targetable mediators of tumour-to-TME communication, including members of the complement component system and the neuropeptide/GPCR ligand-receptor pair ADCYAP1-ADCYAP1R1. These interactions could influence DIPG tumour progression and represent novel therapeutic targets.

Overview

  • The study aimed to investigate the mechanisms of disease progression and oncogenic interactions between diffuse intrinsic pontine glioma (DIPG) tumour cells and the tumour microenvironment (TME) in a single patient.
  • The study used spatial transcriptomic sequencing analysis to identify four distinct tumour subpopulations and assess ligand-receptor pairs that promote DIPG tumour progression through crosstalk with endothelial, neuronal, and immune cell communities.
  • The primary objective of the study was to identify potential targetable mediators of tumour-to-TME communication and novel therapeutic targets for DIPG treatment.

Comparative Analysis & Findings

  • The study identified four distinct tumour subpopulations and assessed respective ligand-receptor pairs that actively promote DIPG tumour progression via crosstalk with endothelial, neuronal, and immune cell communities.
  • The analysis found potential targetable mediators of tumour-to-TME communication, including members of the complement component system and the neuropeptide/GPCR ligand-receptor pair ADCYAP1-ADCYAP1R1.
  • These interactions could influence DIPG tumour progression and represent novel therapeutic targets.

Implications and Future Directions

  • The study provides new insights into the mechanisms of disease progression in DIPG and highlights the potential of targeting tumour-to-TME communication for therapeutic intervention.
  • Future studies should investigate the signalling pathways and biological processes involved in ADCYAP1-ADCYAP1R1-mediated tumour progression and explore its efficacy as a therapeutic target.
  • The study's findings may also inform the development of novel diagnostic biomarkers for DIPG and other brain cancers and could lead to improved patient outcomes.
Read Full Article