Dendritic cells as therapeutic agents against cancer

Eksioglu, Erika A.; Eisen, Seth A.; Reddy,

doi:10.2741/3623

Cited by 14 publications

(13 citation statements)

References 115 publications

(285 reference statements)

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“…In the last decade, protocols for the generation of human monocyte-derived DCs have been established, allowing for analysis of the immunological features of these important APC populations and the successful translation of this knowledge into DC-targeted vaccination studies in various diseases (28,41,42).…”

Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase Modulates Maturation of Human Dendritic Cells

Adler¹,

Simon

Graulich³

et al. 2010

The Journal of Immunology

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Dendritic cells (DCs) are the most potent APCs of the immune system. Understanding the intercellular and intracellular signaling processes that lead to DC maturation is critical for determining how these cells initiate T cell-mediated immune processes. NO synthesized by the inducible NO synthase (iNOS) is important for the function of murine DCs. In our study, we investigated the regulation of the arginine/NO-system in human monocyte-derived DCs. Maturation of DCs induced by inflammatory cytokines (IL-1β, TNF, IL-6, and PGE2) resulted in a pronounced expression of neuronal NOS (nNOS) but only minimal levels of iNOS and endothelial NOS were detected in human mature DCs. In addition, reporter cell assays revealed the production of NO by mature DCs. Specific inhibitors of NOS (N-nitro-l-arginine methyl ester) or of the NO target guanylyl cyclase (H-(1,2,4)-oxadiazolo [4,3-a] quinoxalin-1-one) prevented DC maturation (shown by decreased expression of MHC class II, costimulatory and CD83 molecules and reduced IL-12 production) and preserved an immature phenotype, indicating an autocrine effect of nNOS-derived NO on human DC maturation. Notably, inhibitor-treated DCs were incapable of inducing efficient T cell responses after primary culture and generated an anergic T cell phenotype. In conclusion, our results suggest that, in the human system, nNOS-, but not iNOS-derived NO, plays an important regulatory role for the maturation of DCs and, thus, the induction of pronounced T cell responses.

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Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase Modulates Maturation of Human Dendritic Cells

Adler¹,

Simon

Graulich³

et al. 2010

The Journal of Immunology

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“…Dendritic cells (DC) are commonly used as biologic therapy for cancer because of their physiologic roles in initiating and modulating the host immune response (1,2). In many cases, monocytes obtained from patients by apheresis have been used as a source of DCs (3,4).…”

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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“…In its inchoate stages, immunotherapy has been considered a promising treatment modality for metastatic cancers. Many new strategies have been proposed, including cytokine therapy, 1, 2 dendritic cell-based vaccines, 3,4 and immuneactivating antibodies, 5,6 which have begun to be used in clinical studies, either alone or in various combinations with other therapies. However, so far immunotherapy only has made limited progress in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Assessment of thermal effects of interstitial laser phototherapy on mammary tumors using proton resonance frequency method

Figueroa

et al. 2011

J. Biomed. Opt.

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Abstract. Laser immunotherapy (LIT) uses a synergistic approach to treat cancer systemically through local laser irradiation and immunological stimulation. Currently, LIT utilizes dye-assisted noninvasive laser irradiation to achieve selective photothermal interaction. However, LIT faces difficulties treating deeper tumors or tumors with heavily pigmented overlying skin. To circumvent these barriers, we use interstitial laser irradiation to induce the desired photothermal effects. The purpose of this study is to analyze the thermal effects of interstitial irradiation using proton resonance frequency (PRF). An 805-nm near-infrared laser with an interstitial cylindrical diffuser was used to treat rat mammary tumors. Different power settings (1.0, 1.25, and 1.5 W) were applied with an irradiation duration of 10 min. The temperature distributions of the treated tumors were measured by a 7 T magnetic resonance imager using PRF. We found that temperature distributions in tissue depended on both laser power and time settings, and that variance in tissue composition has a major influence in temperature elevation. The temperature elevations measured during interstitial laser irradiation by PRF and thermocouple were consistent, with some variations due to tissue composition and the positioning of the thermocouple's needle probes. Our results indicated that, for a tissue irradiation of 10 min, the elevation of rat tumor temperature ranged from 8 to 11• C for 1 W and 8 to 15• C for 1.5 W. This is the first time a 7 T magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. Our work provides a basic understanding of the photothermal interaction needed to control the thermal damage inside a tumor using interstitial laser treatment. Our work may lead to an optimal protocol for future cancer treatment using interstitial phototherapy in conjunction with immunotherapy. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Dendritic cells as therapeutic agents against cancer

Cited by 14 publications

References 115 publications

Neuronal Nitric Oxide Synthase Modulates Maturation of Human Dendritic Cells

Neuronal Nitric Oxide Synthase Modulates Maturation of Human Dendritic Cells

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

Assessment of thermal effects of interstitial laser phototherapy on mammary tumors using proton resonance frequency method

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