AUTHOR=Zhang Dong , Ma Yiming , Feng Daxiong 

TITLE=Mapping TAM–tumor crosstalk in glioma via ligand–receptor multi-omics: mechanisms of immune evasion

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1699915

DOI=10.3389/fimmu.2025.1699915

ISSN=1664-3224

ABSTRACT=Diffuse gliomas remain lethal primary brain tumors. Immune-checkpoint inhibitors have not delivered durable benefit for most patients, reflecting myeloid-dominant immunosuppression and spatially organized immune exclusion. In this mini-review we summarize ligand–receptor multi-omics—single-cell RNA/CITE-seq, single-cell chromatin accessibility, and spatial proteo-transcriptomics—that resolve microglia- and monocyte-derived TAM programs and malignant state continua, and we appraise translational opportunities spanning TAM reprogramming (CSF1–CSF1R), perivascular SPP1–CD44 disruption, and innate–adaptive combinations targeting CD47–SIRPα, CD39–CD73, and PD-1/PD-L1. We also discuss challenges—including ontogeny-aware state definitions, heteromer-aware databases, chromatin gating of receivers (requiring accessible regulatory DNA for the receptor and its program), spatial registration, and limited assay standardization—that temper implementation. By integrating myeloid-informed readouts (SPP1–TAM burden, CD39–CD73 proximity, HMOX1+ IL-10 niches, serum IL-8), emerging strategies aim to restore antigen presentation, enable effector ingress, and remodel vascular–stromal interfaces. Our synthesis provides an appraisal of reproducible communication architectures in glioma and outlines pragmatic reporting standards and trial-ready pharmacodynamic endpoints for myeloid-informed precision immuno-oncology. We hope these insights will assist researchers and clinicians as they design multi-omics pipelines and interventions to convert suppressive ecosystems into responsive ones.