Use of interferon-α-induced dendritic cells in the therapy of patients with malignant brain gliomas

Леплина, О. Ю.; Stupak, V. V.; Kozlov, Yu.P.; Pendyurin, I. V.; Никонов, С. Д.; Тихонова, М. А.; Sycheva, N. V.; Ostanin, А. А.; Черных, Е. Р.

doi:10.1007/s10517-007-0172-1

Cited by 14 publications

(13 citation statements)

References 18 publications

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“…Recent studies have shown that dendritic cells (DCs) as innate immunity cells have cytotoxic functions and can suppress tumor cell growth [1–3]. This activity of DCs is mediated through expression of TNF family pro-apoptogenic molecules [1–3] and is enhanced in response to interferons [4, 5].…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis

Сахно¹,

Тихонова²,

Тыринова³

et al. 2012

Clinical and Developmental Immunology

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The PD-1/B7-H1-mediated induction of T cell apoptosis/anergy as a possible mechanism of immune response failure was studied in 76 patients with pulmonary tuberculosis (TB) with normal and low-proliferative response to antigens of M. tuberculosis (purified protein derivative (PPD)). It was revealed that dendritic cells (DCs), generated in vitro from patient blood monocytes with GM-CSF + IFN-α, were characterized by increased B7-H1 expression, upproduction of IL-10, and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). Moreover, DCs of patients with TB were able to enhance T cell apoptosis and to block T-cell division in MLC. It was shown that neutralizing anti-PD1 antibodies significantly decreased the proapoptogenic/tolerogenic effect of DCs. Correlation analysis revealed a direct relationship between IL-10 production and level of B7-H1 expression in the general group of investigated patients. It was demonstrated that generation of healthy donor DCs in the presence of IL-10 led to an increase in the number of DCs-expressed B7-H1 molecule, DC proapoptogenic activity, and a decrease in their allostimulatory activity. Obviously, the revealed phenomenon of the PD-1/B7-H1-mediated pro-apoptogenic activity of DCs is clinically significant since the cytotoxic/tolerogenic potential of DCs is more pronounced in patients with PPD anergy.

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Section: Introductionmentioning

confidence: 99%

“…This activity of DCs is mediated through expression of TNF family pro-apoptogenic molecules [1–3] and is enhanced in response to interferons [4, 5]. It was also shown that DCs are capable of expressing coinhibitory molecule B7-H1, which is a ligand for receptor-programmed cell death 1 (PD-1) [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis

Сахно¹,

Тихонова²,

Тыринова³

et al. 2012

Clinical and Developmental Immunology

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“…To date, there are a number of approaches for generating DCs in vitro, including preparation of DCs from peripheral blood monocytes and bone marrow progenitors (CD34 + cells) (18). Furthermore, a wide range of factors may be used for differentiation and maturation of DCs (GM-CSF, IL-4, interferon-α, IL-2, IL-6, IL-15, TGF-α, stem cell factor, FLT-3 ligand and prostaglandin E2) that may facilitate, in a combination or individually, the generation of DCs from monocytes or CD34 + cells (19)(20)(21)(22)(23). The present study suggested that there is some danger in using numerous factors for differentiation and maturation of DCs that can lead to the production of DC subsets with a variety of phenotypes and functions.…”

Section: Discussionmentioning

confidence: 99%

Use of antigen‑primed dendritic cells for inducing antitumor immune responses inï¿½vitro in patients with non‑small cell lung cancer

Obleukhova

Kiryishina²,

Falaleeva

et al. 2017

Oncol Lett

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Abstract.Cancer is associated with a reduction in immature and mature circulating dendritic cells (DCs), and with an impaired migratory capacity, compared with healthy donors. Therefore, modern approaches to the in vitro generation of DCs loaded with tumor antigens and their use for inducing antitumor immune responses in vivo are being investigated. The purpose of the present study was to investigate the phenotypic and functional characteristics of peripheral blood DC subsets in patients with non-small cell lung cancer (NSCLC), and the development of an antitumor cytotoxic response by mononuclear cells (MNCs) from patients using in vitro generated antigen-primed DCs. Heparinized peripheral venous blood samples were obtained from 10 healthy donors and 20 patients with a histologically verified diagnosis of NSCLC. The ability of antigen-activated DCs to stimulate the activity of MNCs against autologous tumor cells was evaluated using a cytotoxic test. Peripheral blood DC subsets from patients with NSCLC were identified to be decreased and to exhibit an impaired ability to mature, compared with healthy donors. Furthermore, DCs generated from MNCs from patients with NSCLC were able to stimulate a specific cytotoxic response when loaded with autologous tumor lysates or RNA and matured, in vitro. A perforin and granzyme B-dependent mode of cytotoxicity was primarily induced. The ability of DCs loaded with tumor antigens to increase the cytotoxic activity of MNCs against NSCLC cells in vitro indicates the effective induction and co-stimulation of T lymphocytes by the generated DCs.

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“…Actually, IFN-DCs, as compared with the IL-4-induced DCs, are known for their high migration activity, stability in the absence of growth factors and low expression of DC-SIGN molecules, capable of binding M. tuberculosis [7,32]. The major promise of DC vaccines for induction of antigen-specific immune response is actively discussed not only in cancer, but also in chronic infections [33][34][35]. However, the clinical development of therapeutic vaccines for TB patients requires the preliminary testing and in vitro correction of impaired DC functions.…”

Section: Citationmentioning

confidence: 99%

Low Antigen-specific T-cell Response in Pulmonary Tuberculosis is Associated with Impaired Phenotype and Functions of Interferon-α Induced Dendritic Cells

EYa¹

2013

J Clin Cell Immunol

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The phenotype and functions of monocyte-derived dendritic cells (DCs), generated upon stimulation with GM-CSF and IFN-α, were investigated in pulmonary tuberculosis (TB). The most pronounced increase of IL-10 production, as well as the decrease of allostimulatory activity and the alteration of T1/T2 stimulatory activity of DCs were registered in patients with low PPD-induced proliferative response. The data obtained evidence the tolerogenic phenotype of monocyte-derived IFN-DCs and the association of DC impairment with decreased antigen-specific T cell response in TB patients.

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Use of interferon-α-induced dendritic cells in the therapy of patients with malignant brain gliomas

Cited by 14 publications

References 18 publications

Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis

Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis

Use of antigen‑primed dendritic cells for inducing antitumor immune responses inï¿½vitro in patients with non‑small cell lung cancer

Low Antigen-specific T-cell Response in Pulmonary Tuberculosis is Associated with Impaired Phenotype and Functions of Interferon-α Induced Dendritic Cells

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