scholarly journals Cell-Mediated Therapies to Facilitate Operational Tolerance in Liver Transplantation

2021 ◽  
Vol 22 (8) ◽  
pp. 4016
Author(s):  
Samia D. Ellias ◽  
Ellen L. Larson ◽  
Timucin Taner ◽  
Scott L. Nyberg
Keyword(s):  
Liver Transplantation ◽  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Cellular Therapy ◽  
Cell Therapies ◽  
Operational Tolerance ◽  
Regulatory Dendritic Cells ◽  
Parenchymal Cells

Cell therapies using immune cells or non-parenchymal cells of the liver have emerged as potential treatments to facilitate immunosuppression withdrawal and to induce operational tolerance in liver transplant (LT) recipients. Recent pre-clinical and clinical trials of cellular therapies including regulatory T cells, regulatory dendritic cells, and mesenchymal cells have shown promising results. Here we briefly summarize current concepts of cellular therapy for induction of operational tolerance in LT recipients.

scholarly journals Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji-Eun Irene Yum ◽  
Young-Kwon Hong
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Checkpoint Molecule

VISTA is an up-and-coming immune checkpoint molecule that can become the target of new cancer immunotherapy treatments. Immune cells in the tumor microenvironment can largely influence the progression of cancer through inhibitory and stimulatory pathways. Indeed, VISTA is expressed on many immune cells, including T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. VISTA has predominantly been shown to act in an immune-suppressing manner that enables cancer progression. This review will delve into results from preclinical murine studies of anti-VISTA monoclonal antibody treatments, bring together recent studies that detect VISTA expression on immune cells from patient tumors of various cancers, and discuss ongoing clinical trials involving VISTA.

scholarly journals Splenic Stroma-Educated Regulatory Dendritic Cells Induce Apoptosis of Activated CD4 T Cells via Fas Ligand-Enhanced IFN-γ and Nitric Oxide

2011 ◽  
Vol 188 (3) ◽  
pp. 1168-1177 ◽  
Author(s):  
Xiongfei Xu ◽  
Hai Yi ◽  
Zhenhong Guo ◽  
Cheng Qian ◽  
Sheng Xia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Ifn Γ ◽  
Regulatory Dendritic Cells

scholarly journals ILDR1 Is a Prognostic Biomarker and Associated With Immune Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Yanling Ma ◽  
WenBo Qi ◽  
BaoHong Gu ◽  
XueMei Li ◽  
ZhenYu Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Copy Number ◽  
Sequencing Data ◽  
Number Variation ◽  
Gastric Cancer Patients

Abstract Objective: To investigate the association between ILDR1 and prognosis and immune infiltration in gastric cancer. Methods: We analyzed the RNA sequencing data of 9736 tumor tissues and 8587 normal tissues in the TCGA and GTEx databases through the GEPIA2 platform. The expression of ILDR1 in gastric cancer and normal gastric mucosa tissues with GEPIA and TIMER. Clinical subgroup analysis was made through Kaplan-Meier analysis. Analyzed the correlation between ILDR1 and VEGFA expression in gastric cancer, through the gene sequencing data of gastric cancer in TCGA. Explored the relationship between ILDR1 methylation and the prognosis of gastric cancer patients through the MethSurv database. The correlation between ILDR1 and immune cells and the correlation of copy number variation were explored through the TIMER database. Results: ILDR1-high GC patients had a lower PFS and OS. High ILDR1 expression was significantly correlated with tumor grade. There was a negative correlation between the ILDR1 expression and the abundances of CD8+ T, Macrophages and DC and etc. The methylation level of ILDR1 is associated with a good prognosis of gastric cancer. ILDR1 copy number variation was correlated with immune cells, IDLR1 arm-loss was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, and arm-duplication was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. Conclusion: The increased expression of ILDR1 is associated with poor prognosis in patients with gastric cancer. ILDR1 can be used as a novel predictive biomarker to provide a new therapeutic target for gastric cancer patients.

scholarly journals DC-Based Vaccines for Cancer Immunotherapy

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 706
Author(s):  
Chunmei Fu ◽  
Li Zhou ◽  
Qing-Sheng Mi ◽  
Aimin Jiang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Critical Role ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Cell Immunity

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell responses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of antigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos.

Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells

2016 ◽  
Vol 137 (2) ◽  
pp. 426-435 ◽  
Author(s):  
Jae-Uoong Shim ◽  
Shee Eun Lee ◽  
Won Hwang ◽  
Changhon Lee ◽  
Jung-Won Park ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory Dendritic Cells

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

Calreticulin Promotes Immunity Against Acute Myeloid Leukemia Cells in Vivo

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 996-996
Author(s):  
Xiufen Chen ◽  
Dominick Fosco ◽  
Douglas E. Kline ◽  
Justin Kline
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Surface ◽  
Vector Control ◽  
Immune Cells ◽  
Myeloid Leukemia ◽  
Innate Immune ◽  
Innate Immune Cells

Abstract Pre-apoptotic cancer cells release internalized calreticulin (CRT) to their surface prior to death, which acts as an ‘eat-me’ signal to local phagocytes. Chemotherapy and irradiation, which can induce immunogenic cell death through CRT translocation, can also result in local and/or systemic immune suppression in the host. To bypass the requirement of exposing the host to chemotherapy to induce translocation of CRT to the cell surface, murine acute myeloid leukemia (AML) cells (C1498), were engineered to constitutively express cell surface CRT (C1498.CRT). Vector control C1498 or C1498.CRT cells were inoculated intravenously (IV) into C57BL/6 mice. Significantly prolonged survival was observed in hosts harboring C1498.CRT versus vector control C1498 cells systemically. The survival benefit were abrogated in both Rag2-/- hosts or by depletion of T cells with anti-CD4 plus anti-CD8 antibodies, arguing that the immune-mediated effect of cell-surface CRT expression is dependent upon a functional adaptive immune system. More strikingly, systemic inoculation with C1498.CRT cells expressing the model SIYRYYGL (SIY) peptide antigen (C1498.SIY.CRT cells) resulted in almost complete protection from AML development (>90% long term survival vs. 10% of C1498.SIY vector control cells). All animals surviving a primary C1498.SIY.CRT challenge rejected a subsequent re-challenge with C1498.SIY cells, suggesting that CRT-expressing AML cells promote immunologic memory. Significantly enhanced expansion and unregulated IFNγ production were observed among SIY-specific T cell receptor transgenic CD8+ 2C T cells following their adoptive transfer into hosts bearing C1498.SIY.CRT AML cells versus vector control C1498.SIY cells. Interestingly, CRT expression on AML cells did not promote their in vivo phagocytosis by innate immune cells, specifically splenic CD8a+ dendritic cells known to engulf AML cells following their IV inoculation. IL-12 production by CD8α+CD11c+ dendritic cells which had engulfed C1498 and C1498.CRT cells in vivo was similarly induced, and cross-presentation of the SIY antigen to 2C T cells ex vivo by purified CD8a+DCs following in vivo exposure to C1498.SIY or C1498.SIY.CRT cells was also similar. In conclusion, it is clear that expression on CRT on the surface of AML cells leads to robust leukemia-specific T cell activation and expansion resulting in prolonged leukemia-specific survival in AML-bearing animals. Although a direct effect of CRT on innate immune cells, such as dendritic cells, is suspected, the molecular mechanism underlying the “CRT effect” remains unclear, and is being explored further through gene expression analysis in purified DCs which have engulfed CRT-expressing or control AML cells in vivo, as well as in animals genetically deficient in the putative CRT receptor, LRP, in dendritic cells. It will be of interest to analyze spontaneous CRT expression on AML cells from human samples and to correlate cell surface CRT expression with the presence or absence of spontaneous T cell responses to known AML antigens and with clinical outcomes. Disclosures No relevant conflicts of interest to declare.

Biologic meshes in cancer patients: A double-edged sword—Differences in production of IL6 and IL12 caused by acellular dermal matrices in human immune cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3064-3064
Author(s):  
Maria Margarete Guenthner-Biller ◽  
Sabine Enders ◽  
Julia Knabl ◽  
Verena Engelstaedter ◽  
Peter Duewell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Statistical Difference ◽  
Wilcoxon Test ◽  
Dermal Matrices ◽  
Acellular Dermal

3064 Background: Acellular dermal matrices (ADM) have been used in different fields of surgery for almost 20 years. In 2005 Breuing et al first described its use in breast cancer patients. It is assumed that it is safe to use in an oncologic setting, but data from controlled studies are still missing. Because of its lack of cells ADM are considered not to cause an immune reaction. With increasing knowledge about the importance of immunology in breast cancer more information about ADM on different immune cell populations is needed. IL6 and IL12 are two central cytokines and key regulators of immune supression and activation. Methods: Strattice (ST; LifeCell) CollaMend (CM; Bard Davol), Biodesign (BD; Cook Biotec) as well as TiLoop a synthetic mesh (TL; pfm medical) were used in this study. We isolated myeloid dendritic cells (MDC), untouched plasmacytoid dendritic cells (PDC), naïve B-cells and CD8+ T-cells using the MACS System and co-cultered them with the biologic meshes or TL. For positive controls, we used CpG ODN 2216 3 µg/ml and LPS in a concentration of 100 ng/ml. Cytokine concentration of IL12p70 and IL6 were determined after seven days by using sandwich Elisa sets. Statistical significance was determined by the nonparametric Friedman-Test. The single hypothesis was calculated with a paired Wilcoxon Test. Results: There was a highly significant difference between the different ADM and TL in the immunologic response. The statistical difference for IL 6 was p= 0.0006131 for B cells and p= 0.00418 for T cells between TL and ADM. ST also caused significantly more IL6 than CM and BD. We found similar differences in IL 12 with p= 0.00194 for B cells and p= 0.003636 in T cells in regard to the difference between TL and ADM. For IL 12 there was no statistical difference between the ADM. We didn´t see any significant differences in the cytokine profile between the various ADM/TL in the MDC and PDC subpopulations. Conclusions: Despite the assumed lack of immune answer to ADM, immune cells reacted in our study with significantly different cytokine profiles. These findings can have implications regarding the activation or suppression of effector cells in a cancer patient.

scholarly journals Hepatitis B Immunoglobulins Inhibit Dendritic Cells and T Cells and Protect Against Acute Rejection After Liver Transplantation

2005 ◽  
Vol 5 (10) ◽  
pp. 2393-2402 ◽  
Author(s):  
J. Kwekkeboom ◽  
T. Tha-In ◽  
W.M.W. Tra ◽  
W. Hop ◽  
P.P.C. Boor ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cells ◽  
Dendritic Cells ◽  
Hepatitis B ◽  
Acute Rejection

scholarly journals High Mobility Group Box 1 Contributes to the Acute Rejection of Liver Allografts by Activating Dendritic Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Chen ◽  
Wenmin Zhang ◽  
Hui Bao ◽  
Wubing He ◽  
Lihong Chen
Keyword(s):  
Liver Transplantation ◽  
T Cells ◽  
Dendritic Cells ◽  
Acute Rejection ◽  
Allograft Rejection ◽  
High Mobility ◽  
Serum Transaminase ◽  
High Mobility Group ◽  
Therapeutic Effects ◽  
Liver Preservation

Acute rejection induced by the recognition of donor alloantigens by recipient T cells leads to graft failure in liver transplant recipients. The role of high mobility group box 1 (HMGB1), an inflammatory mediator, in the acute allograft rejection of liver transplants is unknown. Here, rat orthotopic liver transplantation was successfully established to analyze the expression pattern of HMGB1 in liver allografts and its potential role in promoting the maturation of dendritic cells (DCs) to promote T cell proliferation and differentiation. Five and 10 days after transplantation, allografts showed a marked upregulation of HMGB1 expression accompanied by elevated levels of serum transaminase and CD3+ and CD86+ inflammatory cell infiltration. Furthermore, in vitro experiments showed HMGB1 increased the expressions of co-stimulatory molecules (CD80, CD83, and MHC class II) on bone marrow-derived DCs. HMGB1-pulsed DCs induced naive CD4+ T cells to differentiate to Th1 and Th17 subsets secreting IFN-γ and IL-17, respectively. Further in vivo experiments confirmed the administration of glycyrrhizic acid, a natural HMGB1 inhibitor, during donor liver preservation had therapeutic effects by reducing inflammation and hepatocyte damage reflected by a decline in serum transaminase and prolonged allograft survival time. These results suggest the involvement of HMBG1 in acute liver allograft rejection and that it might be a candidate therapeutic target to avoid acute rejection after liver transplantation.

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