Myeloid control of dendritic cell priming after mechanical HIFU in colorectal cancer: implications for PD-1/PD-L1 blockade.

Mechanical high-intensity focused ultrasound releases tumor antigens and danger signals. It provides a potential substrate for immune checkpoint blockade. However, antigen release does not necessarily generate productive dendritic cell priming. In colorectal cancer, this transition occurs within a mucosal microenvironment shaped by epithelial barrier integrity, microbial exposure and myeloid clearance. Neutrophils can support epithelial repair or reinforce tumor-associated suppression. Macrophages remove apoptotic granulocytes and regulate inflammatory resolution. They can also restrain dendritic cell cytokine production. These context-dependent functions may determine whether mechanically released antigens initiate cytotoxic immunity or enter a nonproductive clearance response. This mini review integrates intestinal myeloid homeostasis with experimental evidence for mechanical ultrasound ablation and PD-1/PD-L1 blockade. It distinguishes antigen uptake from cross-presentation, protective resolution from tumor-permissive suppression, and colorectal evidence from observations in other tumor models. Functional dendritic cell readouts, lineage-resolved checkpoint measurements and concurrent barrier assessment provide a framework for evaluating combination therapy. The therapeutic objective is to preserve mucosal protection while sustaining antigen-specific immunity.