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Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.

ABSTRACT: IL-15, a pleiotropic cytokine, stimulates generation of NK, NK-T, ??, ILC1, and memory CD8 T cells. IL-15 disorders play pathogenetic roles in organ-specific autoimmune diseases including celiac disease. Diverse approaches are developed to block IL-15 action. IL-15 administered to patients with malignancy yielded dramatic increases in NK numbers and modest increases in CD8 T cells. Due to immunological checkpoints, to achieve major cancer therapeutic efficacy, IL-15 will be used in combination therapy, and combination trials with checkpoint inhibitors, with anti-CD40 to yield tumor-specific CD8 T cells, and with anticancer monoclonal antibodies to increase ADCC and antitumor efficacy, have been initiated.

SUBMITTER: Waldmann TA

PROVIDER: S-EPMC7037239 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.

Waldmann Thomas A TA Miljkovic Milos D MD Conlon Kevin C KC

The Journal of experimental medicine 20200101 1

IL-15, a pleiotropic cytokine, stimulates generation of NK, NK-T, γδ, ILC1, and memory CD8 T cells. IL-15 disorders play pathogenetic roles in organ-specific autoimmune diseases including celiac disease. Diverse approaches are developed to block IL-15 action. IL-15 administered to patients with malignancy yielded dramatic increases in NK numbers and modest increases in CD8 T cells. Due to immunological checkpoints, to achieve major cancer therapeutic efficacy, IL-15 will be used in combination t ...[more]

PMID: 31821442

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Project description:IntroductionA large body of evidence has established a pattern of altered functioning in the immune system, autonomic nervous system and hypothalamic pituitary adrenal axis in chronic fatigue syndrome. However, the relationship between components within and between these systems is unclear. In this paper we investigated the underlying network structure of the autonomic system in patients and controls, and a larger network comprising all three systems in patients alone.MethodsIn a sample of patients and controls we took several measures of autonomic nervous system output during 10 minutes of supine rest covering tests of blood pressure variability, heart rate variability and cardiac output. Awakening salivary cortisol was measured on each of two days with participants receiving 0.5mg dexamethasone during the afternoon of the first day. Basal plasma cytokine levels and the in vitro cytokine response to dexamethasone were also measured. Symptom outcome measures used were the fatigue impact scale and cognitive failures questionnaire. Mutual information criteria were used to construct networks describing the dependency amongst variables. Data from 42 patients and 9 controls were used in constructing autonomic networks, and 15 patients in constructing the combined network.ResultsThe autonomic network in patients showed a more uneven distribution of information, with two distinct modules emerging dominated by systolic blood pressure during active stand and end diastolic volume and stroke volume respectively. The combined network revealed strong links between elements of each of the three regulatory systems, characterised by three higher modules the centres of which were systolic blood pressure during active stand, stroke volume and ejection fraction respectively.ConclusionsCFS is a complex condition affecting physiological systems. It is important that novel analytical techniques are used to understand the abnormalities that lead to CFS. The underlying network structure of the autonomic system is significantly different to that of controls, with a small number of individual nodes being highly influential. The combined network suggests links across regulatory systems which shows how alterations in single nodes might spread throughout the network to produce alterations in other, even distant, nodes. Replication in a larger cohort is warranted.

Dataset Information

Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.

Publications

Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.

Similar Datasets

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