Walid Kamoun, Vice President and Global Head of Reasearch and Development Oncology at Servier, shared on LinkedIn:
“Chronic stress accelerates glioma growth and shortens survival in tumor-bearing mice. Yang et al. report the mechanism in Cancer Cell, and it runs through the bone marrow.
Integrated multi-omics of syngeneic glioma samples identified a stress-induced population the authors call stress-associated macrophages: CD45+CD11b+C5aR1+. Parabiosis experiments established the origin. SAMs derive from bone marrow monocytes, not from resident microglia. The wiring is sympathetic. Stress-activated sympathetic nerve promotes differentiation of ADRB2+ bone marrow monocytes into SAMs. Selective ablation of catecholaminergic nerves antagonizes that differentiation.
Two independent interventions on the complement axis converge: conditional knockout of C5ar1 in macrophages, and pharmacologic C5aR inhibition. Both reduce SAMs and attenuate stress-induced glioma growth in vivo. The functional defect is metabolic. SAMs show elevated CD36 expression, which drives excessive intracellular lipid accumulation and peroxidation, dampening phagocytotic capacity.
Thanks to Yang et al. for this insightful paper.”
Title: Macrophage-mediated brain-bone marrow crosstalk promotes chronic stress-induced glioma growth
Authors: Zhengnan Yang, Jingtian Zhou, Fan Fei, Bohao Zheng, Sophie Xin Yang, Thomas M. Pearce, Peidong Zhang, Liang Huang, Jing Yue, Qiuhong Shen, Yiwei Du, Xiaoling Liao, Siyu Cheng, Li Li, Jian Liang, Luyao Liu, Xiaoxiao Wan, Michael D. Taylor, Joseph R. Ecker, Shengtao Zhou, Jeremy N. Rich, Linjie Zhao
Read the Full Article on Cancer Cell
Other posts featuring Walid Kamoun on OncoDaily.