Dendritic Cells and Immune Checkpoints Within the Tumor Microenvironment: Mechanisms, Models, and Therapy

Dear Colleagues,

Effective cancer immunotherapy depends not only on T-cell reinvigoration but also on the presence and functionality of dendritic cells (DCs) within the native tumor immune microenvironment. Checkpoint blockade and other immunostimulatory agents—such as agonists of STING, CD40, FLT3, or TLR pathways—ultimately rely on intratumoral DCs to capture antigens, mature appropriately, and prime or re-prime effector T-cells. Insufficient numbers or impaired activation of tumor-resident DC subsets have emerged as key barriers to response, while preserved DC niches correlate strongly with therapeutic benefit across cancers. Understanding these DC-dependent mechanisms requires experimental systems that maintain the full complexity of cancer immune infiltrates, including native myeloid, lymphoid, and stromal components.

This Special Issue welcomes studies dissecting how immune checkpoint inhibitors and immunostimulatory agents modulate DC biology, antigen presentation, and T-cell dynamics within tumor ecosystems. We encourage submissions leveraging advanced in situ and ex vivo approaches—such as spatial profiling, organoids retaining endogenous immune populations, and single-cell multi-omics—to reveal how DCs integrate microenvironmental cues and modulate sensitivity or resistance to immunotherapy. Work bridging mechanistic insights with translational or clinical findings is particularly valued.

Dr. Francisco J. Cueto
Guest Editor

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