RT Journal Article
SR Electronic
T1 Immune landscape of isocitrate dehydrogenase stratified human gliomas
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.08.514794
DO 10.1101/2022.11.08.514794
A1 Pravesh Gupta
A1 Minghao Dang
A1 Shivangi Oberai
A1 Mekenzie Peshoff
A1 Nancy Milam
A1 Aml Ahmed
A1 Krishna Bojja
A1 Tuan M. Tran
A1 Kathryn Cox
A1 Huma Shehwana
A1 Carlos Kamiya-Matsuoka
A1 Jianzhuo Li
A1 Joy Gumin
A1 Alicia Goldman
A1 Sameer A. Seth
A1 Atul Maheshwari
A1 Frederick F. Lang
A1 Nicholas E. Navin
A1 Amy B. Heimberger
A1 Karen Clise-Dwyer
A1 Linghua Wang
A1 Krishna P. Bhat
YR 2022
UL http://biorxiv.org/content/early/2022/11/09/2022.11.08.514794.abstract
AB The brain tumor immune microenvironment (TIME) continuously evolves during glioma progression, but only a limited view of a highly complex glioma associated immune contexture across isocitrate dehydrogenase mutation (IDH) classified gliomas is known. Herein, we present an unprecedentedly comprehensive view of myeloid and lymphoid cell type diversity based on our single cell RNA sequencing and spectral cytometry-based interrogation of tumor-associated leukocytes from fifty-five IDH stratified primary and recurrent human gliomas and three non-glioma brains. Our analyses revealed twenty-two myeloid and lymphoid cell types within and across glioma subtypes. Glioma severity correlated with microglial attrition concomitant with a continuum of invading monocyte-derived microglia-like and macrophages amongst other infiltrating conventional T and NK lymphocytes and unconventional mucosa associated invariant T (MAIT) cells. Specifically, certain microglial and monocyte-derived subpopulations were associated with antigen presentation gene modules, akin to cross-presenting dendritic cells (DCs). Furthermore, we identified phagocytosis and antigen presentation gene modules enriched in Triggering receptor expressed on myeloid (TREM)-2+ cells as a putative anti-glioma axis. Accelerated glioma growth was observed in Trem2 deficient mice implanted with CT2A glioma cells affirming the anti-glioma role of TREM2+ myeloid cells. In addition to providing a comprehensive landscape of glioma-specific immune contexture, our investigations discover TREM2 as a novel immunotherapy target for brain malignancies.Competing Interest StatementThe authors have declared no competing interest.