Dendritic Cell Therapeutics in Cancer Immunotherapy

Dendritic cells (DCs) are professional antigen-presenting cells that bridge innate and adaptive immunity by capturing, processing and presenting tumour-derived antigens to T lymphocytes. In DC-based therapies, monocyte-derived or naturally circulating DC subsets are isolated, loaded ex vivo with tumour antigens (peptides, proteins, lysates or mRNA) and matured with toll-like receptor ligands or cytokine cocktails before reinfusion. These vaccines aim to elicit tumour-specific CD8+ cytotoxic T lymphocytes, CD4+ helper T cells and natural killer cell activation, establishing immunological memory. Clinical studies to date have confirmed safety and immunogenicity but limited monotherapy efficacy, largely due to immunosuppressive networks within the tumour microenvironment, including regulatory T cells, myeloid-derived suppressor cells and inhibitory checkpoints (PD-L1, CTLA-4, indoleamine 2,3-dioxygenase). To overcome resistance, DC vaccines are increasingly combined with immune checkpoint blockade, chemotherapy- or radiotherapy-induced immunogenic cell death, local cytokine delivery and novel delivery platforms such as RNA-modified DCs and nanoparticle carriers. These strategies seek to enhance antigen presentation, promote T cell infiltration and reprogram the tumour milieu. The global significance of DC therapeutics lies in their potential for personalised neoantigen targeting, synergy with emerging immunomodulatory agents and applicability across diverse malignancies.

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Dendritic Cell Therapeutics in Cancer Immunotherapy publication trend

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Technical terms

Dendritic cell: A professional antigen-presenting cell that captures antigens, migrates to lymphoid organs and activates naïve T lymphocytes.

Antigen presentation: The process by which peptide fragments bound to major histocompatibility complex molecules are displayed on the surface of antigen-presenting cells for T cell recognition.

Immune checkpoint: A regulatory pathway, such as PD-1/PD-L1 or CTLA-4, that modulates T cell activation and maintains self-tolerance by delivering inhibitory signals.

Tumour microenvironment: The complex ecosystem of cancer cells, stromal elements, immune populations and soluble factors that influence tumour progression and immune evasion.

Ex vivo: Procedures or manipulations performed on cells outside the living organism prior to reinfusion or analysis.

References

1. Clinical Implications of Co-Inhibitory Molecule Expression in the Tumor Microenvironment for DC Vaccination: A Game of Stop and Go. Frontiers in Immunology (2013).
2. Combination Strategies to Optimize Efficacy of Dendritic Cell-Based Immunotherapy. Frontiers in Immunology (2018).
3. From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past. Frontiers in Immunology (2021).
4. CTLA-4 silencing in dendritic cells loaded with colorectal cancer cell lysate improves autologous T cell responses in vitro. Frontiers in Immunology (2022).