Midkine activation of CD8+ T cells establishes a neuron–immune–cancer axis responsible for low-grade glioma growth

Xiaofan Guo, Yuan Pan, Min Xiong, Shilpa Sanapala, Corina Anastasaki, Olivia Cobb, Sonika Dahiya, David H. Gutmann

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Brain tumors (gliomas) are heterogeneous cellular ecosystems, where non-neoplastic monocytic cells have emerged as key regulators of tumor maintenance and progression. However, relative to macrophages/microglia, comparatively less is known about the roles of neurons and T cells in glioma pathobiology. Herein, we leverage genetically engineered mouse models and human biospecimens to define the axis in which neurons, T cells, and microglia interact to govern Neurofibromatosis-1 (NF1) low-grade glioma (LGG) growth. NF1-mutant human and mouse brain neurons elaborate midkine to activate naïve CD8+T cells to produce Ccl4, which induces microglia to produce a key LGG growth factor (Ccl5) critical for LGG stem cell survival. Importantly, increased CCL5 expression is associated with reduced survival in patients with LGG. The elucidation of the critical intercellular dependencies that constitute the LGG neuroimmune axis provides insights into the role of neurons and immune cells in controlling glioma growth, relevant to future therapeutic targeting.

Original languageEnglish
Article number2177
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Fingerprint

Dive into the research topics of 'Midkine activation of CD8+ T cells establishes a neuron–immune–cancer axis responsible for low-grade glioma growth'. Together they form a unique fingerprint.

Cite this