PO.TB10.13 · 肿瘤生物学

Reactive oligodendrocytes promote glioblastoma progression through CCL5/CCR5-mediated glioma stem cell maintenance

编号 6228 展板 9 时间 4/21 02:00–05:00 区域 Section 32 主讲 Jason Moffat, PhD

分会场 Tumor-Neuron Interactions and Neuro-Regulation of Cancer

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作者与单位

Nicholas Mikolajewicz¹, Kui Zhai², Anish Puri², Petar Miletic², Nazanin Tatari², jiarun Wei¹, Neil Savage², Zhi Huang³, Qian Huang³, Seon Yong Lee¹, Mahta Jan-Ahmadnejad⁴, Roseanne Nguyen⁴, David Chen¹, Tiegan Korman², Daniel Mobilio², Maxwell Topley², Jack Qinyu Lu², Matthew R. Voisin², Zsolt Zador², Shawn C. Chafe², Chitra Venugopal², Kevin R. Brown¹, Gelareh Zadeh⁵, Hong Han², Julien Muffat⁴, Shideng Bao³, Sheila K. Singh², Jason Moffat¹

¹Genetics and Genome Biology, Sick Children's Hospital, Toronto, ON, Canada,²McMaster University, Hamilton, ON, Canada,³Cancer Biology, Cleveland Clinic, Cleveland, OH,⁴Neurosciences and Mental Health, Sick Children's Hospital, Toronto, ON, Canada,⁵University Health Network, Toronto, ON, Canada

摘要 Abstract

Glioblastoma (GBM) evolves within a microenvironment abundant in oligodendrocyte-lineage (OL) cells. In this study, we utilized single-cell and spatial transcriptomics from primary and recurrent GBM tumors, immunohistochemistry, cytokine profiling, and migration assays to show that GBM cells recruit OLs to the tumor border via CXC3L1/CXC3R1 signaling. A pan-disease human OL meta-atlas and syngeneic mouse models reveal an interferon-induced reactive OL state, akin to those seen in demyelinating inflammatory and traumatic injury, which is enriched in CNS malignancies. These reactive OLs secrete pro-tumorigenic cytokines, notably CCL5, that promote GBM tumor cell growth through CCR5 signaling. CCR5 is preferentially expressed in glioma stem-like cells (GSCs) and upregulated at recurrence. Targeting CCR5 with genetic knockdown or FDA-approved drug Maraviroc impairs GSC stemness and prolongs survival in GBM models. Our work highlights the functional interplay between OLs and GBM cells and positions the CCL5/CCR5 axis as a druggable target in GBM.

利益披露 Disclosure

N. Mikolajewicz, None.. K. Zhai, None.. A. Puri, None.. P. Miletic, None.. N. Tatari, None.. J. Wei, None.. Z. Huang, None.. Q. Huang, None.. S. Lee, None.. M. Jan-Ahmadnejad, None.. R. Nguyen, None.. D. Chen, None.. T. Korman, None.. D. Mobilio, None.. M. Topley, None.. J. Lu, None.. M. R. Voisin, None.. Z. Zador, None.. S. C. Chafe, None.. C. Venugopal, None.. K. R. Brown, None.. G. Zadeh, None.. H. Han, None.. J. Muffat, None.. S. Bao, None.. S. K. Singh, None.. J. Moffat, None.

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