Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients

Millán, Olga; Rafael-Valdivia, L.; Torrademé, E.; Lopez, Anna Lena; Fortuna, Virginia; Sánchez‐Cabús, Santiago; López-Púa, Yolanda; Rimola, Antoni; Brunet, Mercè

doi:10.1016/j.cyto.2012.10.026

Cited by 66 publications

(42 citation statements)

References 23 publications

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“…A pre-transplant cut-off value of 55.8% for CD8 + IFN-γ + identified patients at high risk of acute rejection (specificity, 82%; sensitivity, 75%). In the first week following transplantation, patients with a percentage of inhibition for (35). In the present study, NK cells, were more active in patients with higher IFN-γ, who have a higher-risk of rejection, than those with a lower IFN-γ density.…”

Section: Discussionmentioning

confidence: 56%

Role of natural killer cells in liver transplantation treatment of liver cancer

Jin

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Liver cancer caused by diet or life style is a significant public health problem. Liver transplantation (LT) is a commonly used method of treatment for the liver cancer. The present study aimed to determine whether assessing the net state of natural killer (NK) cell function following LT distinguishes patients at risk for transplantation rejection. A total of 53 patients were involved; all underwent LT for hepatocellular carcinoma with (n=13) or without (n=40) transplantation rejection. The density of interferon-γ (IFN-γ) in blood serum was examined and patients were divided into two groups: Higher (H) and lower (L), on the basis of IFN-γ density. The percentage of NK cells and their producing cytokines was detected using fluorescence-activated cell sorting in peripheral blood and liver samples. As evaluation indexes of liver function, aspartate transaminase (AST) and alanine transaminase (ALT) were detected in blood serum. NK cell activation of the H-group was observed to be higher than the L-group, specifically the expression of NK group 2D, cluster of differentiation 69 and IFN-γ were higher than the L-group. The H-group exhibited a higher level of AST and ALT, which indicates the potential for acute transplantation rejection. The results of the present study indicate that NK cells and NK-derived IFN-γ serve an important function in regulating the rejection of LT and tumor metastasis in response to LT.

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Section: Discussionmentioning

confidence: 56%

Role of natural killer cells in liver transplantation treatment of liver cancer

Jin

et al. 2017

Experimental and Therapeutic Medicine

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“…In a study of immunosuppression drug weaning in stable long-term liver transplant recipients, Millán et al showed that soluble IFN-γ and intracellular IFN-γ and IL-2 were significantly increased in patients who rejected, suggesting that these biomarkers may prove useful to identify patients at high risk of AR (Millán et al 2010). In addition, this group have also observed that pre-and post-transplantation evaluation of intracellular expression of IFN-γ on CD4+ and IFN-γ and IL-2 on CD8 + T cells could identify de novo liver transplant patients with a high risk of AR and high susceptibility to immunosuppressive treatment (Millán et al 2013). Furthermore, several studies in kidney transplant recipients have shown that high frequencies of donor reactive memory T cells are associated with increased IFN-γ production, a high risk of AR in the early posttransplantation period, and poorer first-year graft function (Nickel et al 2004;Kim et al 2007;Bestard et al 2008).…”

Section: Intracellular Cytokine Staining (Ics)mentioning

confidence: 93%

“…FC has also become a useful tool to evaluate the pharmacodynamic effect of immunosuppressive therapy in order to determine the real biologic effect of specific drugs or drug combinations in the recipient. The upregulation of cytokine production and activation of surface receptors of T cells lead to T-cell proliferation, a key step during AR (Millán et al 2013;Carey et al 2007).…”

Section: Potential Applications To Prognosis Other Diseases or Condmentioning

confidence: 96%

Flow Cytometry as Platform for Biomarker Discovery and Clinical Validation

Millán¹,

Brunet²

2015

Biomarkers in Disease: Methods, Discoveries and Applications

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“…The ability to secrete cytokines is critical in determining whether T cells are activated when they recognize an alloantigen (30). Monitoring the secretion of major cytokines, including IFN-γ and IL-2 by CD4 + and CD8 + T cells, could be useful in determining the immune response to stimulation with DCs.…”

Section: Discussionmentioning

confidence: 99%

Dendritic cells loaded with the lysate of tumor cells infected with Newcastle Disease Virus trigger potent anti‑tumor immunity by promoting the secretion of IFN‑γ and IL‑2 from T cells

et al. 2018

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Abstract. Dendritic cells (DCs) are professional antigenpresenting cells that are pivotal in the generation and sustainability of antitumor immune responses. Whole tumor cell lysates (TCLs) have been used as sources of tumor antigens for the development of DC vaccines. However, the clinical outcomes of the use of TCL-based DC vaccines have so far been unsatisfactory because of the weak immunogenicity of tumor cells. To improve the efficacy of TCL-based DC vaccines, viruses have been used to enhance the immunity of TCLs and to further enhance the antigen delivery and antigen-presenting ability of DCs. The aim of the present study was to improve the antigen-presenting ability of DCs and to use them to effectively activate T lymphocytes. The present study demonstrated that DCs loaded with the lysate of Newcastle Disease Virus (NDV)-infected tumor cells (NDV-TCL) have increased levels of cluster of differentiation 80 (CD80), CD86, CD83 and human leukocyte antigen-antigen D-associated expression, compared with those loaded with TCL alone. The DCs loaded with the NDV-TCL promoted T-cell proliferation and antitumor cytokine secretion from T cells. These results indicated that loading DCs with NDV-TCL could enhance the antigen-presenting ability of the DCs. On the basis of the results of the present study, we hypothesize that this method of loading DCs with NDV-TCL can be used to develop novel DC vaccines for tumor immunotherapy in the future. IntroductionDendritic cells (DCs) are the most important antigen-presenting cells in the body; DC-based cancer immunotherapy has been investigated in previous years (1-4). Additionally, the approval of the first DC vaccine, Provenge (generic name, sipuleucel-T) (5), by the US Food and Drug Administration for the treatment of prostate cancer in 2010 was a milestone in the immunotherapeutic application of DC vaccines. Whole-tumor cell lysates (TCLs) have been used as the source of tumor antigens for the development of DC vaccines; however, the clinical outcomes of TCL-based DC vaccines have been unsatisfactory owing to the weak immunogenicity of tumor cells (6). To improve the efficacy of TCL-based DC vaccines, viruses have been used to enhance the immunity of TCLs, to further enhance the antigen delivery and to increase the antigen-presenting ability of DCs (7).The Newcastle Disease Virus (NDV) is a bird RNA virus of the Paramyxovirus family. Specifically, NDV belongs to the genus Avulavirus, which does not include any known natural pathogens of humans (8). Over the last 6 decades, NDV has been tested as an anticancer agent because of its oncolytic properties. Owing to the oncolytic and immunostimulatory properties of NDV, necrotic tumor cells destroyed by the virus are phagocytosed and perceived as dangerous by antigen-presenting cells. These professional antigen-presenting cells then process tumor-associated antigens (TAA), become activated and present the processed TAA peptides to T cells for cognate interaction and the induction of an immune response. Owing to NDV's properties ...

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Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients

Cited by 66 publications

References 23 publications

Role of natural killer cells in liver transplantation treatment of liver cancer

Role of natural killer cells in liver transplantation treatment of liver cancer

Flow Cytometry as Platform for Biomarker Discovery and Clinical Validation

Dendritic cells loaded with the lysate of tumor cells infected with Newcastle Disease Virus trigger potent anti‑tumor immunity by promoting the secretion of IFN‑γ and IL‑2 from T cells

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