Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma

Favreau, Mérédis; Menu, Eline; Gaublomme, Djoere; Vanderkerken, Karin; Faict, Sylvia; Maes, Ken; Bruyne, Elke De; Govindarajan, Srinath; Drennan, Michael; Calenbergh, Serge Van; Leleu, Xavier; Zabeau, Lennart; Tavernier, Jan; Venken, Koen

doi:10.1038/leu.2017.146

Cited by 25 publications

(27 citation statements)

References 40 publications

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“…Given their restricted TCR usage, this strategy can also be explored for MAIT cells (MAIT-CAR). Another important obstacle is the observation of functional exhaustion of iNKT, which has also been shown for MAIT cells [113,114]. For instance, administration of soluble iNKT ligands have been linked to the upregulation of inhibitory co-stimulatory molecules such as PD-1 [115].…”

Section: A Role For Mait Cells In Cancer Immunotherapy?mentioning

confidence: 99%

MAIT Cells Come to the Rescue in Cancer Immunotherapy?

Łukasik

Elewaut

Venken

2020

Cancers

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Recent progress in immunobiology has led to the observation that, among cells classically categorized as the typical representatives of the adaptive immune system, i.e., T cells, some possess the phenotype of innate cells. Invariant T cells are characterized by T cell receptors recognizing a limited range of non-peptide antigens, presented only in the context of particular molecules. Mucosal-associated invariant T cells (MAIT cells) are an example of such unconventional cells. In humans, they constitute between 1% and 8% of the peripheral blood T lymphocytes and are further enriched in mucosal tissues, mesenteric lymph nodes, and liver, where they can account for even 40% of all the T cells. MAIT cells recognize antigens in the context of major histocompatibility complex class I-related protein (MR1). Upon activation, they instantly release pro-inflammatory cytokines and mediate cytolytic function towards bacterially infected cells. As such, they have been a rapidly evolving research topic not only in the field of infectious diseases but also in the context of many chronic inflammatory diseases and, more recently, in immuno-oncology. Novel findings suggest that MAIT cells function could also be modulated by endogenous ligands and drugs, making them an attractive target for therapeutic approaches. In this review, we summarize the current understanding of MAIT cell biology, their role in health and disease and discuss their future potential in cancer immunotherapy. This is discussed through the prism of knowledge and experiences with invariant natural killer T cells (iNKT)—another prominent unconventional T cell subset that shares many features with MAIT cells.

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Section: A Role For Mait Cells In Cancer Immunotherapy?mentioning

confidence: 99%

MAIT Cells Come to the Rescue in Cancer Immunotherapy?

Łukasik

Elewaut

Venken

2020

Cancers

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“…Получены данные, свидетельствующие о повышении уровня лептина в сыворотке крови и содержания рецептора лептина на iNKT-клетках периферической крови и костного мозга больных ММ по сравнению с условно здоровыми донорами [112]. Результаты экспериментов по совместному культивированию iNKT-клеток, стимулированных лигандом CD1d α-галактозилцерамидом (α-GalCer), и миеломных клеток показали, что добавление лептина в среду приводит к значительному снижению способности iNKT-клеток секретировать IFN-γ.…”

Section: клетки иммунной системыunclassified

“…Результаты экспериментов по совместному культивированию iNKT-клеток, стимулированных лигандом CD1d α-галактозилцерамидом (α-GalCer), и миеломных клеток показали, что добавление лептина в среду приводит к значительному снижению способности iNKT-клеток секретировать IFN-γ. Более того, блокирование с помощью антител рецептора лептина на iNKT-клетках способствует усилению их активации и продукции IFN-γ и TNF-α, что сопровождается развитием выраженного иммунного ответа на клетки миеломы у экспериментальных животных [112].…”

Section: клетки иммунной системыunclassified

Bone marrow adipocytes and multiple myeloma

Фильченков

2019

Onkogematologiâ

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Multiple myeloma originating from clonal proliferation of plasma cells in the bone marrow is one of the most prevalent hematological malignancies worldwide. The pathogenetic mechanisms of multiple myeloma are far from being elucidated. Nevertheless, it is known that the adipocytes as the prevalent cellular component of bone marrow microenvironment contribute significantly to multiple myeloma growth and progression. The review discloses the recent data on the interactions between bone marrow adipocytes and myeloma cells, hematopoietic stemcells, hematopoietic progenitor cells, mesenchimal stem cells, osteoblasts, osteoclasts, endothelial cells, and cells of immune system. Also, the review places special emphasis on bone marrow adipocyte-produced adipokines, growth factors, cytokines, chemokines, and fatty acids providing the conditions for the preferential growth and migration of malignant plasma cells and contributing to hematopoiesis supression, bone tissue resorption, angiogenesis activation and immunosuppression.

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“…Furthermore, during obesity, adipocytes produce the adipokine leptin to flag nutrient excess and diminish food intake. Leptin contributes to an iNKT cell response that results in anergy and PD-1 upregulation by directly triggering the leptin receptor expressed by iNKT cells ( 76 , 77 ). Importantly, leptin-mediated iNKT cell activation still requires TCR triggering ( 77 ).…”

Section: Immunometabolic Inkt Cell Activationmentioning

confidence: 99%

Immunometabolic Activation of Invariant Natural Killer T Cells

et al. 2018

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Invariant natural killer T (iNKT) cells are lipid-reactive T cells with profound immunomodulatory potential. They are unique in their restriction to lipid antigens presented in CD1d molecules, which underlies their role in lipid-driven disorders such as obesity and atherosclerosis. In this review, we discuss the contribution of iNKT cell activation to immunometabolic disease, metabolic programming of lipid antigen presentation, and immunometabolic activation of iNKT cells. First, we outline the role of iNKT cells in immunometabolic disease. Second, we discuss the effects of cellular metabolism on lipid antigen processing and presentation to iNKT cells. The synthesis and processing of glycolipids and other potential endogenous lipid antigens depends on metabolic demand and may steer iNKT cells toward adopting a Th1 or Th2 signature. Third, external signals such as toll-like receptor ligands, adipokines, and cytokines modulate antigen presentation and subsequent iNKT cell responses. Finally, we will discuss the relevance of metabolic programming of iNKT cells in human disease, focusing on their role in disorders such as obesity and atherosclerosis. The critical response to metabolic changes places iNKT cells at the helm of immunometabolic disease.

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Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma

Cited by 25 publications

References 40 publications

MAIT Cells Come to the Rescue in Cancer Immunotherapy?

MAIT Cells Come to the Rescue in Cancer Immunotherapy?

Bone marrow adipocytes and multiple myeloma

Immunometabolic Activation of Invariant Natural Killer T Cells

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