12–15 However, cDC1s are rare (<0.2%–0.3%) in peripheral blood mononuclear cells (PBMCs), and isolating a sufficient number of cDC1s for repeated therapeutic vaccination is difficult. There is a growing body of evidence that cDC1s have the superior capacity to cross-present exogenous antigen to CD8 T cells, produce IL-12 in response to innate and T cell–derived stimuli, induce Th1-type T cell responses, and play a critical role in antitumor T-cell responses. Of the different naturally occurring DCs, the Batf3-dependent conventional type 1 DC (cDC1) subset represents a promising alternative to monocyte-derived DCs for vaccination purposes. 2–4 Compelling evidence indicates that naturally occurring (primary) DC subsets are phenotypically and transcriptionally distinct from ex vivo–generated monocyte-derived DCs. 2 Although numerous clinical studies using monocyte-derived DC have showed DC vaccination has low toxicity and induces tumor-specific immune responses, the number of objective clinical responses is limited. 1 DC-based immunotherapy has been tested for harnessing the potential of a patient’s own immune system however, which subsets of DCs can be used to design efficient vaccines remains to be determined. Human iPSC-derived DCs have phagocytic, T-cell proliferative, and cytokine-producing functions.ĭendritic cells (DCs) are a diverse population of specialized antigen-presenting cells that link innate and adaptive immunity, and crucial in the induction of immune responses to pathogens and tumors as well as for the maintenance of self-tolerance. Notch-activated human iPSC-derived XCR1 CLEC9A HLA-DR CD11c cells exhibited similar gene expression profile with peripheral blood cDC1s. Inhibition of Notch signaling during co-culture of iPSC-derived CD34 hematopoietic progenitor cells with OP9-DL1 cells abrogated generation of cDC1s, cDC2As, cDC2Bs, CD5 cDC2s, and AS-DCs but increased frequency of DC3s. Plasmacytoid DCs were not differentiated from iPSCs on either OP9 or OP9-DL1 cells. ![]() Results Flow cytometric analyses and single-cell profiling of HLA-DR cells revealed that human iPSCs gave rise to CD141 XCR1 CLEC9A cells (cDC1s), CLEC4A hiCLEC10A –CD1c cells (cDC2As), CLEC4A loCLEC10A CD1c cells (cDC2Bs), CD163 –CD5 CD1c cells (CD5 cDC2s), and AXL SIGLEC6 cells (AS-DCs) on OP9 feeder cells expressing the Notch ligand delta-like 1 (OP9-DL1) while the majority of iPSC-derived cells differentiated on OP9 cells were CD163 CD5 –CD1c cells (DC3s) and monocytes. 8 Department of Surgery, University of Southern California, Los Angeles, CA, USA.7 Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.6 Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.5 Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.4 Department of Surgery, Shinshu University Graduate School of Medicine School of Medicine, Matsumoto, Nagano, Japan.3 Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.2 Department of Obstetrics and Gynecology, Akita University Graduate School of Medicine School of Medicine, Akita, Japan. ![]()
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