Spatial omics insights into tumor myeloid cells: roles in tumorigenesis, prognosis, and therapy

Tumor-associated myeloid cells form a highly plastic and spatially organized immune compartment that plays a central role in tumor evolution, clinical outcome, and therapeutic response. Single-cell RNA sequencing has revealed extensive heterogeneity among macrophages, monocytes, neutrophils, dendritic cells, and related lineages, uncovering transcriptional programs linked to tumor promotion or immune activation. However, the dissociative nature of single-cell approaches disrupts tissue architecture, limiting insight into how myeloid cells interact with malignant, stromal, and lymphoid populations within intact tumors. Recent advances in spatial omics technologies address this limitation by preserving tissue context while enabling high-dimensional profiling of RNA and protein expression in situ. In this review, we synthesize emerging spatial proteomic and transcriptomic studies of tumor-associated myeloid cells, identify recurrent spatial architectures that govern tumorigenesis, prognosis, and treatment response, and examine analytical frameworks that translate spatial patterns into mechanistic understanding. By moving beyond descriptive spatial maps, we highlight unifying biological principles and translational opportunities that position myeloid spatial organization as a critical determinant of cancer progression and precision oncology.