Targeting Dendritic Cells in Cancer Immunotherapy: From Immune Priming to Tumor Microenvironment Reprogramming
- 1Hematology-Oncology and Stem-Cell Transplantation Unit, Department of Onco-Hematology and Innovative Diagnostics, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, IRCCS, 80131 Napoli, Italy
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.
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BibTeX
@article{zanotta2026targeting,
title = {{Targeting Dendritic Cells in Cancer Immunotherapy: From Immune Priming to Tumor Microenvironment Reprogramming}},
author = {Serena Zanotta and Domenico Galati},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219607},
url = {https://www.mdpi.com/1422-0067/27/21/9607},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeting Dendritic Cells in Cancer Immunotherapy: From Immune Priming to Tumor Microenvironment Reprogramming
AU - Serena Zanotta
AU - Domenico Galati
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219607
UR - https://www.mdpi.com/1422-0067/27/21/9607
AB - 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.
SN - 1422-0067
ER -