Dendritic cells in cancer immunotherapy

Schuler, Gerold

doi:10.1002/eji.201040630

Cited by 99 publications

(88 citation statements)

References 103 publications

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“…In many cases, monocytes obtained from patients by apheresis have been used as a source of DCs (3,4). However, the number of monocytes obtained from peripheral blood, their ability to differentiate into DCs, and the quality of the resulting DCs vary among patients.…”

Section: Introductionmentioning

confidence: 99%

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Zhang

Liu

Senju

et al. 2015

Cancer Immunology Research

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The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture. In this study, we generated mouse proliferating myeloid cells (pMC) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DC) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80, and CD86. In addition, exposure to maturation stimuli induced the production of TNFα and IL12p70, and enhanced the expression of MHC-II, CD40, and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow–derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2Kb-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs. Cancer Immunol Res; 3(6); 668–77. ©2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Zhang

Liu

Senju

et al. 2015

Cancer Immunology Research

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“…While delivering DEC-205 targeted antigen in conjugation with DC activation/maturation agents (such as anti-CD40 mAb, poly I:C and LPS) has been reported to result in a potent immune response [6][7][8][9][10][11][12], targeting DEC-205 in the absence of such maturation signals has been described to result in T-cell tolerance [13][14][15]. The development of vaccines able to access DCs, thereby eliciting more efficient immune responses, is one of the aims of immune therapy starting from the recent past [16,17]. Clinical trials have been conducted, with limited success, using DCs expanded in culture, loaded with tumor antigens and then re-administered to cancer patients [18].…”

Section: Introductionmentioning

confidence: 99%

Vaccination with filamentous bacteriophages targeting DEC‐205 induces DC maturation and potent anti‐tumor T‐cell responses in the absence of adjuvants

et al. 2011

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The efficacy of a new vaccine-delivery vector, based on the filamentous bacteriophage fd displaying a single-chain antibody fragment known to bind the mouse DC surface molecule DEC-205, is reported. We demonstrate both in vitro and in vivo an enhanced receptormediated uptake of phage particles expressing the anti-DEC-205 fragment by DCs. We also report that DCs targeted by fd virions in the absence of other stimuli produce IFN-a and IL-6, and acquire a mature phenotype. Moreover, DC-targeting with fd particles double-displaying the anti-DEC-205 fragment on the pIII protein and the OVA [257][258][259][260][261][262][263][264] antigenic determinant on the pVIII protein induced potent inhibition of the growth of the B16-OVA tumor in vivo. This protection was much stronger than other immunization strategies and similar to that induced by adoptively transferred DCs. Since targeting DEC-205 in the absence of DC activation/maturation agents has previously been described to result in tolerance, the ability of fd bacteriophages to induce a strong tumor-specific immune response by targeting DCs through DEC-205 is unexpected, and further validates the potential employment of this safe, versatile and inexpensive delivery system for vaccine formulation.

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“…Ex vivo-generated monocyte-derived DCs (MoDCs) have been tested as therapeutic tumor vaccines in various clinical trials, and several results indicated safety and immunogenicity of these vaccines and, in some cases, increased survival of patients in late disease stages (1,3). It is evident, however, that the DC-based tumor vaccines are expected to improve in overall efficacy (1,4,5). MoDCs, when injected into patients, showed surprisingly little migratory potential (6,7).…”

mentioning

confidence: 99%

Dendritic Cell Reprogramming by Endogenously Produced Lactic Acid

Nasi

Fekete

Krishnamurthy

et al. 2013

The Journal of Immunology

153

118

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The demand for controlling T cell responses via dendritic cell (DC) vaccines initiated a quest for reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce inflammatory or suppressor programs during differentiation, and we identified a powerful autocrine pathway that, in a cell concentration–dependent manner, strongly interferes with inflammatory DC differentiation. MoDCs developing at low cell culture density have superior ability to produce inflammatory cytokines, to induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no inflammatory cytokines upon activation. DCs from high-density cultures maintained more differentiation plasticity and can develop to osteoclasts. The cell concentration–dependent pathway was independent of peroxisome proliferator–activated receptor γ (PPARγ), a known endogenous regulator of MoDC differentiation. Instead, it acted through lactic acid, which accumulated in dense cultures and induced an early and long-lasting reprogramming of MoDC differentiation. Our results suggest that the lactic acid–mediated inhibitory pathway could be efficiently manipulated in developing MoDCs to influence the immunogenicity of DC vaccines.

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Dendritic cells in cancer immunotherapy

Cited by 99 publications

References 103 publications

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Vaccination with filamentous bacteriophages targeting DEC‐205 induces DC maturation and potent anti‐tumor T‐cell responses in the absence of adjuvants

Dendritic Cell Reprogramming by Endogenously Produced Lactic Acid

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