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.