dendritic cell

Overview

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) of the innate immune system that serve as critical sentinels bridging innate sensing and adaptive immunity. First characterized by Ralph Steinman in the 1970s, DCs are distributed throughout peripheral tissues, lymphoid organs, and mucosal surfaces, where they continuously sample the microenvironment for pathogen- and danger-associated molecular patterns. Upon encountering antigenic stimuli, DCs undergo a maturation process marked by upregulation of co-stimulatory molecules, cytokine production, and migration to draining lymph nodes, where they prime naïve T cells, initiate cytotoxic T-lymphocyte responses, and shape the quality of adaptive immunity. Conventional DC subsets (cDC1 and cDC2) are distinguished by distinct transcription factor dependencies and functional specializations: cDC1s excel at cross-presenting exogenous antigens on MHC class I molecules to activate cytotoxic CD8+ T cells, while cDC2s preferentially activate CD4+ T helper cells. Plasmacytoid DCs represent a third major subset specialized for rapid type I interferon production in response to viral nucleic acids sensed through toll-like receptors such as TLR7/8 and TLR9. Beyond their immunostimulatory roles, DCs are equally capable of enforcing peripheral tolerance, and dysregulated DC function underlies a spectrum of diseases including autoimmunity, chronic inflammation, cancer immune evasion, and metabolic disorders.

At the molecular level, DC activation involves pattern recognition receptor signaling through pathways including the cGAS-STING pathway and TLR cascades, leading to nuclear factor kappa B activation, proinflammatory cytokine secretion (interleukin-6, Interleukin 1 beta, IL-12), and cross-presentation of tumor-associated antigens to drive cytotoxic T cell responses. The tumor microenvironment frequently suppresses DC function through immunosuppressive mediators such as TGFB1, prostaglandin E2, and hypoxia-inducible factor-1α, and restoring or enhancing DC activity has become a central strategy in cancer immunotherapy, autoimmune disease management, and vaccine development.

Focus of Latest Publications

Recent publications have continued to position dendritic cells as central orchestrators of immune activation and tolerance across both infectious disease and cancer settings. In food allergy, dietary lactic acid was reported to alleviate ovalbumin-induced allergic symptoms in mice by targeting dendritic cells, suppressing ovalbumin uptake and presentation by bone-marrow-derived dendritic cells and thereby promoting adaptive immune tolerance. In the same study, lactic acid reduced type 2 immune responses, lowered OVA-specific IgE and mast cell protease-1, and decreased IL-4, IL-5, and IL-13 after restimulation, consistent with dendritic cell-mediated reprogramming of immune sensing.

Several recent cancer immunotherapy studies focused on enhancing dendritic cell recruitment, maturation, or antigen-presenting function to strengthen antitumor immunity. A DC-targeted Bacillus Calmette-Guérin vaccine engineered to bind the DEC-205 receptor improved uptake by skin-resident dendritic cell subsets, increased MHC-II expression on vaccine-site myeloid cells, and generated higher frequencies of multifunctional CD4+ T cells, resulting in improved and sustained protection against Mycobacterium tuberculosis in mice. In tumor models, a GM-CSF-expressing irradiated liver cancer cell vaccine activated dendritic cells in lymph nodes and spleen, enhanced dendritic cell maturation and migration, and promoted T-cell differentiation toward cytotoxic and memory phenotypes; oxidized mitochondrial DNA and GM-CSF were reported to synergize in activating the cGAS-STING pathway and supporting dendritic cell activation and antigen presentation.

Other studies used nanotechnology to directly modulate dendritic cells within the tumor microenvironment. A strand-displacement DNA nanomachine selectively targeted tumor-infiltrating dendritic cells through a DC-SIGN-binding aptamer and silenced St6Gal1, restoring dendritic cell function and increasing intratumoral T-cell infiltration while suppressing melanoma growth in mice. A purpurin-copper nanoplatform for colorectal cancer was reported to enhance dendritic cell maturation and T-cell priming while converting immunologically cold tumors into T cell-inflamed phenotypes. Similarly, a dual-peptide, ultrasound-assisted nanoplatform and a multivalent aptamer-drug hybrid both promoted dendritic cell maturation or recruitment alongside broader antitumor immune activation, including increased CD8+ T-cell infiltration and improved responses to checkpoint blockade.

Dendritic cell biology also appeared in studies of immunogenic cell death and inflammatory signaling. A combined ipilimumab and 2-methoxyestradiol nanoplatform induced immunogenic cell death and autophagic cell death to drive dendritic cell activation and maturation while reducing regulatory T-cell infiltration. Another nanoparticle system designed to trigger ferroptosis and a type I interferon response noted that accumulated lipid droplets could inhibit dendritic cell maturation, thereby limiting downstream CD8+ T-cell responses and helping control excessive inflammation. Across these reports, dendritic cells were repeatedly implicated as key intermediates linking antigen exposure, innate sensing, and the generation of effective T-cell immunity.

Key Publications

• NEWJun Dietary Lactic Acid Attenuates Ovalbumin-Induced Food Allergy in Mice via Orchestrating Dendritic Cell and T Cell Immune Tolerance. (Journal of agricultural and food chemistry, 2026, PMID 42287222): "Mechanistically, LA targeted dendritic cells (DCs), suppressing OVA uptake and presentation by bone-marrow-derived DCs."
• Jun Targeted delivery of the BCG vaccine to dendritic cells improves protective efficacy against Mycobacterium tuberculosis. (Vaccine, 2026, PMID 42172693): "we hypothesised that BCG interacts sub-optimally with dendritic cells (DCs), key mediators of adaptive immunity."
• Apr Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review. (Stem cell research & therapy, 2026, PMID 42010708): "Dendritic cells (DCs), belonging to antigen-presenting cells (APCs), are present in different parts of the body with the fundamental activity against tumors and various inflammatory conditions."
• Apr A "one-two punch" strategy to reverse immunosuppressive metabolism and activate T-cell immunity for enhanced cancer checkpoint immunotherapy. (Journal of nanobiotechnology, 2026, PMID 41975460): "2-ME acts to reverse immunosuppression by inhibiting the HIF-1α/HK2 axis and induces immunogenic cell death (ICD) and autophagic cell death (ACD) for antigen exposure and dendritic cell (DC) activation."
• Apr Ratio-Tunable Dual-Peptide and Ultrasound-Assisted Nanoplatform for Enhancing Personalized Antitumor Immunotherapy. (Advanced materials (Deerfield Beach, Fla.), 2026, PMID 41979280): "ultrasound-activated BiNPs with a selected peptide ratio enhance dendritic cell maturation, shift macrophages toward an M1-like phenotype, increase CD8+ T cell infiltration, and suppress primary and distant tumors with favorable biosafety."
• Apr Dual-Targeting Multivalent Aptamer-Drug Hybrids for Synergistic Cancer Immunotherapy. (Journal of the American Chemical Society, 2026, PMID 41973478): "This coordinated action remodels the immunosuppressive tumor microenvironment, promoting dendritic cell recruitment and activation, expanding IFN-responsive macrophages and conventional dendritic cells, and driving the proliferation and functional maintenance of cytotoxic CD8+ T cells."
• Apr Irradiated Liver Cancer Cell Vaccine Transfected With GM-CSF Induces Specific and Long-Lasting Anti-tumour Immunity Through the Synergistic Effect of Oxidised mtDNA and GM-CSF. (Cell proliferation, 2026, PMID 41947668): "Hepa 1-6-mGM-CSF immunisation robustly activated dendritic cells (DCs) and T cells in both lymph nodes and spleen, characterised by enhanced DC maturation and migration, as well as the differentiation of T cells toward cytotoxic and memory phenotypes."
• Apr Engineered Bacillus Calmette-Guérin Mediated Immunotherapy of Triple-Negative Breast Cancer. (ACS nano, 2026, PMID 41949057): "BCG acts as a potent immune initiator, significantly enhancing the recruitment of M1-type macrophages and natural killer cells to the tumor site, and also induced the maturation of dendritic cells."
• Apr A Strand-Displacement Enabled DNA Nanomachine for Targeted St6Gal1 Silencing and Immune Reprogramming in Melanoma. (ACS nano, 2026, PMID 41889102): "Here, we develop an intelligent DNA nanomachine that selectively targets dendritic cells (DCs) within the tumor microenvironment and modulates their immunological function through regulation of prosaposin glycosylation."
• May Lipid droplet-regulated multipathway-induced type I interferon tempest for ferroptosis-immune synergistic therapy of tumors. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41692047): "the accumulated lipid droplets are associated with the inhibition of the maturation of dendritic cells and then the expression of CD8+ T cells without affecting the expression of memory T cells."