Myeloid-driven immunosuppression in head and neck cancer: single-cell ATAC/RNA and spatial transcriptomic perspectives
Year: 2025
Type: article
Abstract: Head and neck squamous cell carcinoma (HNSCC) remains a prevalent epithelial malignancy. Immune-checkpoint inhibitors have reshaped first-line therapy for recurrent/metastatic disease; yet durable benefit is confined to a subset, reflecting myeloid-centric mechanisms—SPP1 + TAM barriers, cDC1/IL-12 insufficiency, and CXCL8–CXCR1/2–driven neutrophil trafficking—distinct from, and complementary to, classical lymphoid exhaustion. In this review we summarize advances from single-cell RNA and ATAC profiling and spatial transcriptomics that resolve macrophage, dendritic-cell and neutrophil programs, and appraise translational opportunities spanning myeloid reprogramming, innate–adaptive combinations and spatial biomarkers. We also discuss enduring challenges—including HPV-status heterogeneity, limited assay standardization and a scarcity of predictive metrics—that temper implementation. By integrating myeloid-informed readouts (e.g., SPP1–TAM burden, cDC1 competency, serum IL-8) with PD-1–based regimens, EGFR-directed antibodies and myeloid checkpoints (CD47–SIRPα, PI3Kγ, CXCR1/2), emerging strategies aim to restore antigen presentation, improve lymphocyte trafficking and remodel tumor–stroma interfaces. Our synthesis provides an appraisal of the evolving landscape of myeloid-informed precision immuno-oncology in HNSCC and outlines pragmatic standards and avenues for clinical translation. We hope these insights will assist researchers and clinicians as they endeavor to implement more effective, individualized regimens.
Source: Frontiers in Oncology
Authors: Rui Luo, Jianzheng Yang, Zimeng Cao, Bing Li
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4417449030