Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol

Kverneland, Anders Handrup; Streitz, Mathias; Geissler, Edward K.; Hutchinson, James A.; Vogt, Katrin; Boës, David; Niemann, Nadja; Pedersen, Anders Elm; Schlickeiser, Stephan; Sawitzki, Birgit

doi:10.1002/cyto.a.22855

Cited by 79 publications

(96 citation statements)

References 73 publications

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“…If immunotherapy is to become a viable option in the treatment of cancer, this imbalance in favor of tumor growth needs to be addressed. CD4 + CD25 + FOXP3 + Tregs account for 5-10% of all T lymphocytes in healthy individuals (23). Evidence suggests that Tregs contribute to immune suppression by dampening the antitumor immunity elicited by CD4 + T cells, CD8 + T cells, dendritic and NK cells (24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P<0.05) concomitant with a significant decrease in Tregs (P<0.01) at 2 weeks post-infusion of CIK cells compared with the baseline. NK group 2D receptor (NKG2D) expression on NK cells was also significantly increased at 2 weeks post-infusion compared with the baseline (P<0.05). There was a positive correlation between NKG2D expression and the infusion number of CIK cells (P<0.05).

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Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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“…They designed a panel of six tubes (seven to nine colors) and had those prepared as dried reagents formulated per single test. Later, they performed a single laboratory study reporting age and gender differences on a cohort of 98 healthy adults (49). Later, they performed a single laboratory study reporting age and gender differences on a cohort of 98 healthy adults (49).…”

Section: Existing Efforts To Achieve Reproducibilitymentioning

confidence: 99%

“…A detailed guide to their approach was published in 2016 (24). Later, they performed a single laboratory study reporting age and gender differences on a cohort of 98 healthy adults (49). The Canadian National Transplant Research Program (CNTRP) adopted The ONE study panels and performed a follow-up study using the dried reagents in which the CNTRP compared sample preparation variables (PBMC versus immediate vs. 24-h delayed staining) and developed and benchmarked an automated analysis approach (35).…”

Section: Existing Efforts To Achieve Reproducibilitymentioning

confidence: 99%

Reproducibility of Flow Cytometry Through Standardization: Opportunities and Challenges

Kalina

2019

Cytometry Pt A

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There is an agreement in the field that interlaboratory reproducibility of flow cytometry measurements as well as the whole studies might be improved by a consensual use of methodological approach. Typically, a consensus is made on a crucial markers needed in the immunostaining panel, sometimes on the particular fluorochrome conjugates and rarely on a complete set of methods for sample preparation. The term "standardization" is used to describe the complete set of methodical steps, while "harmonization" is used for partial agreement on the method. Standardization can provide a platform for improved reproducibility of cytometry results over prolonged periods of time, across different sites and across different instruments. For the purpose of structured discussion, several desired aims are described: common interpretation of the immunophenotype definition of a target subset, accurate quantification, reproducible pattern of a multicolor immunophenotype, and reproducible intensity of all measured parameters. An overview of how standardization was approached by several large consortia is provided: EuroFlow, The ONE Study, Human Immunology Project Consortium (HIPC), and several other groups. Their particular aims and the tools adopted to reach those aims are noted. How those standardization efforts were adopted in the field and how the resulting outcome was evaluated is reviewed. Multiple challenges in the instrument hardware design, instrument setup tools, reagent design, and quality features need to be addressed to achieve optimal standardization. Furthermore, the aims of different studies vary, and thus, the reasonable requirements for standardization differ. A framework of reference for the reasonable outcomes of different approaches is offered. Finally, it is argued that complete standardization is important not only for the reproducibility of measurements but also for education, for quality assessment and for algorithmic data analysis. The different standardized approaches can and in fact should serve as benchmarking reference tools for the development of future flow cytometry studies.

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“…There have already been a few studies which show changes in different immune cell subsets according to age and gender. For example, in a study published by Kverneland et al, an increased proportion of effector and memory CD4 1 and CD8 1 T cells in older patients and a higher CD4 1 : CD8 1 ratio in female patients was observed [59]. Also, there has been evidence that females have higher peripheral levels of T cells with a demethylated TSDR (Niemann et al, unpublished).…”

Section: Limitations Of Assays and Biomarkersmentioning

confidence: 95%

“…Along the same lines, we know that immune cell composition and function changes with age and is different between men and women [59,[167][168][169][170]. However, many biomarkers lack validation according to age and gender specificity.…”

Section: Limitations Of Assays and Biomarkersmentioning

confidence: 99%

Immune monitoring as prerequisite for transplantation tolerance trials

Sani

Sawitzki

2017

Clinical and Experimental Immunology

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SummaryEver since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of ISinduced side effects, which are contributing to the still unsatisfactory longterm graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients. These approaches are based on (i) IS withdrawal in spontaneous operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and (iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing these approaches show that tolerance induction does not work in all patients. Thus, there is a need for reliable biomarkers, which can be used for patient selection and post-therapeutic immune monitoring of safety, success and failure. In this review, we summarize recent achievements in the identification and validation of such immunological assays and biomarkers, focusing mainly on kidney and liver transplantation. From the published findings so far, it has become clear that indicative biomarkers may vary between different therapeutic approaches applied and organs transplanted. Also, patient numbers studied so far are very small. This is the main reason why nearly all described parameters lack validation and reproducibility testing in large clinical trials, and are therefore not yet suitable for clinical practice.

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Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol

Cited by 79 publications

References 73 publications

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Reproducibility of Flow Cytometry Through Standardization: Opportunities and Challenges

Immune monitoring as prerequisite for transplantation tolerance trials

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