Work

Targeting Dendritic Cells in Cancer Immunotherapy: From Immune Priming to Tumor Microenvironment Reprogramming

Year: 2026

Type: article

Abstract: Dendritic cells (DCs) are specialized antigen-presenting cells that shape antitumor immunity by integrating antigen uptake, processing, presentation, co-stimulation, and cytokine-mediated T-cell instruction. Their function is therefore critical for generating tumor-specific T-cell responses and may influence responsiveness to immune checkpoint inhibitors. Although early ex vivo DC vaccines established feasibility, safety, and immunogenicity, clinical efficacy has been heterogeneous. Sipuleucel-T demonstrated an overall-survival benefit in metastatic castration-resistant prostate cancer, whereas DCVax-L produced encouraging but methodologically debated survival signals in glioblastoma. More recently, individualized neoantigen mRNA vaccination combined with pembrolizumab has shown durable recurrence-free survival benefit in resected high-risk melanoma. This review examines the biological rationale for DC-directed immunotherapy, tumor-induced DC dysfunction, next-generation DC platforms, in vivo DC targeting, DC-derived extracellular vesicles, negative and controversial clinical evidence, and rational combinations with checkpoint blockade and tumor-microenvironment-modulating strategies. The field is evolving from the use of DCs as cellular vaccine vehicles toward programmable immune-priming approaches that integrate antigen quality, DC functional state, spatial organization, and tumor microenvironment features.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27219607

Authors: Serena Zanotta, Domenico Galati

Institution: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499