Extracorporeal Photopheresis Efficiently Impairs the Proinflammatory Capacity of Human 6-Sulfo LacNAc Dendritic Cells

Gerner, Michael Y.; Hölig, Kristina; Wehner, Rebekka; Zhao, Senming; Schäkel, Knut; Bachmann, Michael; Rieber, Ernst Peter; Bornhäuser, Martin; Schmitz, Marc

doi:10.1097/tp.0b013e31819e02d4

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…We observed that neither aGVHD response nor aGVHD‐free survival were associated with cell doses even when the hematologic counts or apheresis yield were divided into quartiles, confirming literature reports . A possible explanation is given by studies showing how the cell type (the number of dendritic cells or the number of regulatory T cells generated) can affect the GVHD response; therefore, it appears evident that the biologic response is probably the key affecting the response, something this study indirectly confirms.…”

Section: Discussionsupporting

confidence: 86%

“…The mechanism of action of ECP in GVHD is not fully understood. It has been proposed that ECP modulates host effector cells, including CD8+ T‐lymphocytes, natural killer cells, and circulating antigen‐presenting cells, leading to an attenuation of host antigen‐presenting activity and thus to the development of tolerance . In particular, an elegant study revealed that ECP induces a high percentage of processed monocytes to enter the antigen‐presenting dendritic cell (DC) differentiation pathway, within a single day, as determined by enhanced expression of over 1000 genes, independent of disease state, supporting the concept that, in the future, the ECP might represent a source of DC …”

Section: Discussionmentioning

confidence: 99%

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Extracorporeal photopheresis for graft‐versus‐host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome—results from a large single‐center study

et al. 2014

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BackgroundExtracorporeal photopheresis (ECP) has been shown as active therapy for graft-versus-host disease (GVHD).Study Design and MethodsThe aim was to ascertain the role of ECP in 71 patients with steroid-refractory or -dependent acute and chronic GVHD (aGVHD and cGVHD) with special focus on hematologic variables and GVHD staging classification. A total of 34 patients were treated for aGVHD and 37 for cGVHD.ResultsThe overall response rate (ORR) for aGVHD was 65% and the complete aGVHD-free survival was 50% (95% confidence interval [CI], 36%-70%). The ORR for cGVHD response was 81% while the complete cGVHD-free survival was 50% (95% CI, 34%-73%). The aGVHD-free survival was associated with aGVHD grading (Grade II 81%, Grade III 33%, and Grade IV 0%, p ≤ 0.00) and the absence of visceral involvement (77% vs. 33%, p = 0.03). The cGVHD-free survival was associated with the female sex (67% vs. 25%, p = 0.01) and with the limited form according to the Seattle classification (67% vs. 20%, p = 0.003). No role for hematologic values or apheresis cell count was found, except for the cGVHD ORR (p = 0.037). Transplant-related mortality and overall survival were associated with ECP response 0% versus 54% (p = 0.0001) and 77% versus 45% (p = 0.03) for aGVHD patients and 7% versus 14% (p = 0.02) and 73% versus 20% (p = 0.0003) for cGVHD patients, respectively.ConclusionsWhile confirming a higher probability of GVHD responses for early GVHD, our study shows no role of hematologic values or apheresis cell count on GVHD response.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Extracorporeal photopheresis for graft‐versus‐host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome—results from a large single‐center study

et al. 2014

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“…Even before dying, human DC treated with 8-methoxypsoralen and UVA, promote Th2-biased responses and decrease drastically their ability to drive Th1 polarization [107, 108]. Once reinfused, the ECP-treated leukocytes are retained primarily in the spleen and liver [100, 101], likely by internalization by tissue-resident macrophages and immature DC, as shown for UV-B-irradiated splenocytes injected i.v.…”

Section: Role Of Apoptotic Cells In Extracorporeal Photopheresis In Tmentioning

confidence: 99%

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

Morelli

Larregina

2010

Apoptosis

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One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation.

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“…However, slanDCs have been rarely considered a matter of interest in the allogeneic HSCT setting, in spite of their potential role in the pathogenesis of GVHD [for their induction of T helper type 1 (Th1) immune response and production of TNF‐α in response to LPS], GVL (for their ability to promote tumour cytotoxicity and NK cell activation) and in the first defence against infections during early post‐transplant (for their interaction with neutrophils and NK cells). In fact, to the best of our knowledge, only one study has previously evaluated the reconstitution of slanDCs in patients' PB (although limited to the first 100 days post‐allogeneic HSCT) , while only indirect evidence of the role played by circulating slanDCs in chronic GVHD (cGVHD) was available at the beginning of our study .…”

Section: Introductionmentioning

confidence: 99%

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Mimiola

Marini

Perbellini

et al. 2014

Clinical and Experimental Immunology

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SummaryThe role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD.

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Extracorporeal Photopheresis Efficiently Impairs the Proinflammatory Capacity of Human 6-Sulfo LacNAc Dendritic Cells

Abstract: These novel findings indicate that ECP efficiently impairs the proinflammatory capacity of slanDCs, which may represent an important mechanism for the therapeutic efficiency of ECP in GVHD.

Cited by 14 publications

References 21 publications

Extracorporeal photopheresis for graft‐versus‐host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome—results from a large single‐center study

Extracorporeal photopheresis for graft‐versus‐host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome—results from a large single‐center study

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

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