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1.  Monitoring NK cell activity in patients with hematological malignancies 
Oncoimmunology  2013;2(9):e26011.
Natural killer (NK) cells are lymphocytes of the innate immune system that can recognize and kill various types of malignant cells. Monitoring the activity of peripheral NK cells in patients affected by hematological malignancies may provide prognostic information or unveil ongoing tumor-specific immune responses. Moreover, further insights into the biology of NK cells might also promote the development of novel strategies for stimulating their anticancer activity. Here, we review the main methods to monitor phenotypic and functional NK cell properties in cancer patients, focusing on individuals affected by multiple myeloma, a hematological malignancy currently treated with immunomodulatory drugs.
doi:10.4161/onci.26011
PMCID: PMC3850490  PMID: 24327939
Lenalidomide; cytotoxicity; flow cytometry; multiple myeloma; natural killer cells
2.  Regulation of Mouse NK Cell Development and Function by Cytokines 
Natural Killer (NK) cells are innate lymphocytes with an important role in the early defense against intracellular pathogens and against tumors. Like other immune cells, almost every aspects of their biology are regulated by cytokines. Interleukin (IL)-15 is pivotal for their development, homeostasis, and activation. Moreover, numerous other activating or inhibitory cytokines such as IL-2, IL-4, IL-7, IL-10, IL-12, IL-18, IL-21, Transforming growth factor-β (TGFβ) and type I interferons regulate their activation and their effector functions at different stages of the immune response. In this review we summarize the current understanding on the effect of these different cytokines on NK cell development, homeostasis, and functions during steady-state or upon infection by different pathogens. We try to delineate the cellular sources of these cytokines, the intracellular pathways they trigger and the transcription factors they regulate. We describe the known synergies or antagonisms between different cytokines and highlight outstanding questions in this field of investigation. Finally, we discuss how a better knowledge of cytokine action on NK cells could help improve strategies to manipulate NK cells in different clinical situations.
doi:10.3389/fimmu.2013.00450
PMCID: PMC3859915  PMID: 24376448
natural killer cells; cytotoxicity; interferons; signal transduction; interleukin-15; interleukin-12; interleukin-18; TGF-beta
3.  Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling 
Genome Biology  2008;9(1):R17.
Genome-wide expression profiling of mouse and human leukocytes reveal conserved transcriptional programs of plasmacytoid or conventional dendritic cell subsets.
Background
Dendritic cells (DCs) are a complex group of cells that play a critical role in vertebrate immunity. Lymph-node resident DCs (LN-DCs) are subdivided into conventional DC (cDC) subsets (CD11b and CD8α in mouse; BDCA1 and BDCA3 in human) and plasmacytoid DCs (pDCs). It is currently unclear if these various DC populations belong to a unique hematopoietic lineage and if the subsets identified in the mouse and human systems are evolutionary homologs. To gain novel insights into these questions, we sought conserved genetic signatures for LN-DCs and in vitro derived granulocyte-macrophage colony stimulating factor (GM-CSF) DCs through the analysis of a compendium of genome-wide expression profiles of mouse or human leukocytes.
Results
We show through clustering analysis that all LN-DC subsets form a distinct branch within the leukocyte family tree, and reveal a transcriptomal signature evolutionarily conserved in all LN-DC subsets. Moreover, we identify a large gene expression program shared between mouse and human pDCs, and smaller conserved profiles shared between mouse and human LN-cDC subsets. Importantly, most of these genes have not been previously associated with DC function and many have unknown functions. Finally, we use compendium analysis to re-evaluate the classification of interferon-producing killer DCs, lin-CD16+HLA-DR+ cells and in vitro derived GM-CSF DCs, and show that these cells are more closely linked to natural killer and myeloid cells, respectively.
Conclusion
Our study provides a unique database resource for future investigation of the evolutionarily conserved molecular pathways governing the ontogeny and functions of leukocyte subsets, especially DCs.
doi:10.1186/gb-2008-9-1-r17
PMCID: PMC2395256  PMID: 18218067

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