Cabeza-Cabrerizo, M., Cardoso, A., Minutti, C. M., Pereira da Costa, M. & Reis, E. S. C. Dendritic cells revisited. Annu. Rev. Immunol. 39, 131–166 (2021).
Wculek, S. K. et al. Dendritic cells in cancer immunology and immunotherapy. Nat. Rev. Immunol. 20, 7–24 (2020).
Eisenbarth, S. C. Dendritic cell subsets in T cell programming: location dictates function. Nat. Rev. Immunol. 19, 89–103 (2019).
Sun, L., Su, Y., Jiao, A., Wang, X. & Zhang, B. T cells in health and disease. Signal Transduct. Target. Ther. 8, 235 (2023).
Xie, N. et al. Neoantigens: promising targets for cancer therapy. Signal Transduct. Target. Ther. 8, 9 (2023).
Perez, C. R. & De Palma, M. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 10, 5408 (2019).
Najafi, S. & Mortezaee, K. Advances in dendritic cell vaccination therapy of cancer. Biomed. Pharmacother. 164, 114954 (2023).
Harari, A., Graciotti, M., Bassani-Sternberg, M. & Kandalaft, L. E. Antitumour dendritic cell vaccination in a priming and boosting approach. Nat. Rev. Drug Discov. 19, 635–652 (2020).
Garg, A. D. et al. Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell-driven rejection of high-grade glioma. Sci. Transl. Med. 8, 328ra327 (2016).
Miga, A. J. et al. Dendritic cell longevity and T cell persistence is controlled by CD154–CD40 interactions. Eur. J. Immunol. 31, 959–965 (2001).
Bazewicz, C. G., Dinavahi, S. S., Schell, T. D. & Robertson, G. P. Aldehyde dehydrogenase in regulatory T-cell development, immunity and cancer. Immunology 156, 47–55 (2019).
Zaman, T. S. et al. Notch balances TH17 and induced regulatory T cell functions in dendritic cells by regulating Aldh1a2 expression. J. Immunol. 199, 1989–1997 (2017).
Xiao, S. et al. Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of TH17 cells by enhancing TGF-β-driven SMAD3 signaling and inhibiting IL-6 and IL-23 receptor expression. J. Immunol. 181, 2277–2284 (2008).
Mucida, D. et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256–260 (2007).
La, C. et al. The RNA-binding protein tristetraprolin regulates RALDH2 expression by intestinal dendritic cells and controls local Treg homeostasis. Mucosal Immunol. 14, 80–91 (2021).
Shiokawa, A., Kotaki, R., Takano, T., Nakajima-Adachi, H. & Hachimura, S. Mesenteric lymph node CD11b− CD103+ PD-L1High dendritic cells highly induce regulatory T cells. Immunology 152, 52–64 (2017).
Takaki, H. et al. STAT6 inhibits TGF-β1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. J. Biol. Chem. 283, 14955–14962 (2008).
Manicassamy, S. et al. Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat. Med. 15, 401–409 (2009).
Broadhurst, M. J. et al. Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. PLoS Pathog. 8, e1002883 (2012).
Soroosh, P. et al. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance. J. Exp. Med. 210, 775–788 (2013).
Devalaraja, S. et al. Tumor-derived retinoic acid regulates intratumoral monocyte differentiation to promote immune suppression. Cell 180, 1098–1114 (2020).
Warren, E. W. & Khanderia, U. Use of retinoids in the treatment of psoriasis. Clin. Pharm. 8, 344–351 (1989).
Green, S. G. & Piette, W. W. Successful treatment of hypertrophic lupus erythematosus with isotretinoin. J. Am. Acad. Dermatol. 17, 364–368 (1987).
Esposito, M., Amory, J. K. & Kang, Y. The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes. J. Exp. Med. 221, e20240519 (2024).
Helft, J. et al. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c+MHCII+ macrophages and dendritic cells. Immunity 42, 1197–1211 (2015).
Jin, D. & Sprent, J. GM-CSF culture revisited: preparation of bulk populations of highly pure dendritic cells from mouse bone marrow. J. Immunol. 201, 3129–3139 (2018).
Czuba, L. C., Zhong, G., Yabut, K. C. & Isoherranen, N. Analysis of vitamin A and retinoids in biological matrices. Methods Enzymol. 637, 309–340 (2020).
Vassalli, G. Aldehyde dehydrogenases: not just markers, but functional regulators of stem cells. Stem Cells Int. 2019, 3904645 (2019).
Rhinn, M. & Dolle, P. Retinoic acid signalling during development. Development 139, 843–858 (2012).
Esposito, M. et al. Development of retinoid nuclear receptor pathway antagonists through targeting aldehyde dehydrogenase 1A3. iScience 28, 113675 (2025).
Zhu, B. et al. IL-4 and retinoic acid synergistically induce regulatory dendritic cells expressing Aldh1a2. J. Immunol. 191, 3139–3151 (2013).
Thangavelu, G. et al. Dendritic cell expression of retinal aldehyde dehydrogenase-2 controls graft-versus-host disease lethality. J. Immunol. 202, 2795–2805 (2019).
Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17–27 (1994).
Shortall, K., Djeghader, A., Magner, E. & Soulimane, T. Insights into aldehyde dehydrogenase enzymes: a structural perspective. Front. Mol. Biosci. 8, 659550 (2021).
Lassen, N. et al. Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1−/−/Aldh1a1−/− knock-out mice. J. Biol. Chem. 282, 25668–25676 (2007).
Ohoka, Y., Yokota-Nakatsuma, A., Maeda, N., Takeuchi, H. & Iwata, M. Retinoic acid and GM-CSF coordinately induce retinal dehydrogenase 2 (RALDH2) expression through cooperation between the RAR/RXR complex and Sp1 in dendritic cells. PLoS ONE 9, e96512 (2014).
Dillon, S. et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J. Clin. Invest 116, 916–928 (2006).
Wang, J. et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat. Med. 25, 656–666 (2019).
Inaba, K. et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 176, 1693–1702 (1992).
Kirkling, M. E. et al. Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells. Cell Rep. 23, 3658–3672 (2018).
Choi, Y., Sunkara, V., Lee, Y. & Cho, Y. K. Exhausted mature dendritic cells exhibit a slower and less persistent random motility but retain chemotaxis against CCL19. Lab Chip 22, 377–386 (2022).
Kajino, K., Nakamura, I., Bamba, H., Sawai, T. & Ogasawara, K. Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation. Immunology 120, 28–37 (2007).
Langenkamp, A., Messi, M., Lanzavecchia, A. & Sallusto, F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat. Immunol. 1, 311–316 (2000).
Lawless, S. J. et al. Glucose represses dendritic cell-induced T cell responses. Nat. Commun. 8, 15620 (2017).
Hatfield, P. et al. Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J. Immunother. 31, 620–632 (2008).
Maier, B. et al. A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 580, 257–262 (2020).
Maria, C. C. C. et al. Identification of antigen-presenting cell–T cell interactions driving immune responses to food. Science 387, eado5088 (2025).
Hong, Y. et al. β-Catenin promotes regulatory T-cell responses in tumors by inducing vitamin A metabolism in dendritic cells. Cancer Res. 75, 656–665 (2015).
Truckenbrod, E. N. et al. CD8+ T cell self-tolerance permits responsiveness but limits tissue damage. eLife 10, e65615 (2021).
Ho, P. C. et al. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 162, 1217–1228 (2015).
DePeaux, K. & Delgoffe, G. M. Metabolic barriers to cancer immunotherapy. Nat. Rev. Immunol. 21, 785–797 (2021).
De Leo, A. et al. Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma. Immunity 57, 1105–1123 (2024).
Moller, S. H., Wang, L. & Ho, P. C. Metabolic programming in dendritic cells tailors immune responses and homeostasis. Cell Mol. Immunol. 19, 370–383 (2022).
Klein Geltink, R. I. et al. Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy. Nat. Metab. 2, 703–716 (2020).
Adamik, J. et al. Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients. Nat. Commun. 14, 7211 (2023).
Adamik, J. et al. Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells. Nat. Commun. 13, 5184 (2022).
Amiel, E. et al. Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J. Immunol. 189, 2151–2158 (2012).
Hughes, N. E. et al. Identification of potent and selective retinoic acid receptor γ (RARγ) antagonists for the treatment of osteoarthritis pain using structure based drug design. Bioorg. Med. Chem. Lett. 26, 3274–3277 (2016).
Schulze, G. E. et al. BMS-189453, a novel retinoid receptor antagonist, is a potent testicular toxin. Toxicol. Sci. 59, 297–308 (2001).
Vasiliou, V., Bairoch, A., Tipton, K. F. & Nebert, D. W. Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics 9, 421–434 (1999).
McLean, M. E. et al. The expanding role of cancer stem cell marker ALDH1A3 in cancer and beyond. Cancers 15, 492 (2023).
Zhang, C. et al. Oncorequisite role of an aldehyde dehydrogenase in the pathogenesis of T-cell acute lymphoblastic leukemia. Haematologica 106, 1545–1558 (2021).
Vellozo, N. S. et al. All-trans retinoic acid promotes an M1- to M2-phenotype shift and inhibits macrophage-mediated immunity to Leishmania major. Front. Immunol. 8, 1560 (2017).
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
Sastry, G. M., Adzhigirey, M., Day, T., Annabhimoju, R. & Sherman, W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des. 27, 221–234 (2013).
Harder, E. et al. OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. J. Chem. Theory Comput 12, 281–296 (2016).
Perez-Riverol, Y. et al. The PRIDE Database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2022).
Yurekten, O. et al. MetaboLights: open data repository for metabolomics. Nucleic Acids Res. 52, D640–D646 (2024).


















Leave a Reply