SOCS-mediated immunomodulation of natural killer cells

Keating, Narelle; Nicholson, Sandra E.

doi:10.1016/j.cyto.2018.03.033

Cited by 25 publications

(24 citation statements)

References 94 publications

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“…Additive effects were also observed when CIS-deficiency was combined with targeted immunotherapies such as BRAF and MEK inhibitors, immune checkpoint blockade antibodies, or IFN-I treatment (192). These data suggest that CIS represents a promising target in immunotherapy especially in combination with other immunomodulatory agents (185).…”

Section: Socs Proteinsmentioning

confidence: 99%

“…Immunomodulatory effects of SOCS proteins on NK cells have been reported and suggest them as attractive candidates for immunotherapies (185). SOCS1, 2, 3 and CIS are rapidly induced upon cytokine (57, 186) or GH (187) stimulation.…”

Section: Socs Proteinsmentioning

confidence: 99%

“…SOCS1, 2, 3 and CIS are rapidly induced upon cytokine (57, 186) or GH (187) stimulation. In contrast, little is known about the residual family members SOCS 4-7 that are constitutively expressed in unstimulated cells (185). SOCS4 and SOCS5 are crucial regulators of anti-viral immunity in the context of influenza infection (188, 189).…”

Section: Socs Proteinsmentioning

confidence: 99%

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JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation

et al. 2019

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Natural Killer (NK) cells are cytotoxic lymphocytes of the innate immune system and play a critical role in anti-viral and anti-tumor responses. NK cells develop in the bone marrow from hematopoietic stem cells (HSCs) that differentiate through common lymphoid progenitors (CLPs) to NK lineage-restricted progenitors (NKPs). The orchestrated action of multiple cytokines is crucial for NK cell development and maturation. Many of these cytokines such as IL-2, IL-7, IL-12, IL-15, IL-21, IL-27, and interferons (IFNs) signal via the Janus Kinase / Signal Transducer and Activator of Transcription (JAK/STAT) pathway. We here review the current knowledge about these cytokines and the downstream signaling involved in the development and maturation of conventional NK cells and their close relatives, innate lymphoid cells type 1 (ILC1). We further discuss the role of suppressor of cytokine signaling (SOCS) proteins in NK cells and highlight their potential for therapeutic application.

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Section: Socs Proteinsmentioning

confidence: 99%

Section: Socs Proteinsmentioning

confidence: 99%

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JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation

et al. 2019

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“…Two members of the suppressor of cytokine signaling (SOCS) family, CIS and SOCS2, are reported to control NK cell differentiation and activity ( 128 ). Importantly, CIS serves as a novel checkpoint in NK cell-mediated anti-tumor responses by targeting IL-15 signaling.…”

Section: Checkpoint Molecules In Nk Cell Activationmentioning

confidence: 99%

Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells

Kim

2018

Front. Immunol.

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Among the most promising therapeutic modalities for cancer treatment is the blockade of immune checkpoint pathways, which are frequently co-opted by tumors as a major mechanism of immune escape. CTLA-4 and PD-1 are the representative examples, and their blockade by therapeutic antibodies leads to enhanced anti-tumor immunity with durable clinical responses, but only in a minority of patients. This has highlighted the need to identify and target additional immune checkpoints that can be exploited to further enhance immune responses to refractory cancers. These emerging targets include natural killer (NK) cell-directed checkpoint receptors (KIR and CD94/NKG2A) as well as the NK- and T cell-expressed checkpoints TIM-3, TIGIT, CD96, and LAG-3. Interestingly, the potentiation of anti-tumor immunity by checkpoint blockade relies not only on T cells but also on other components of the innate immune system, including NK cells. NK cells are innate lymphoid cells that efficiently kill tumor cells without MHC specificity, which is complementary to the MHC-restricted tumor lysis mediated by cytotoxic T cells. However, the role of these immune checkpoints in modulating the function of NK cells remains unclear and somewhat controversial. Unraveling the mechanisms by which these immune checkpoints function in NK cells and other immune cells will pave the way to developing new therapeutic strategies to optimize anti-tumor immunity while limiting cancer immune escape. Here, we focus on recent findings regarding the roles of immune checkpoints in regulating NK cell function and their potential application in cancer immunotherapy.

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“…Apart from positive signals, IL-2 and IL-15 also induce the expression of negative regulators to prevent excessive responses. For example, the suppressors of cytokine signaling (SOCS) proteins (CIS, SOCS1) inhibit the JAK enzymatic activity via directly binding to JAK1, JAK2 and TYK2, to form a negative feedback loop limiting the cytokine signaling, thus SOCS protein has been considered as a novel checkpoint for NK cell immunotherapy [57,58].…”

Section: Common Downstream Pathways Of Il-2 and Il-15 Receptorsmentioning

confidence: 99%

Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy

Yang

Lundqvist

2020

Cancers

104

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The type I cytokine family members interleukin-2 (IL-2) and IL-15 play important roles in the homeostasis of innate and adaptive immunity. Although IL-2 and IL-15 receptor complexes activate similar signal transduction cascades, triggering of these receptors results in different functional activities in lymphocytes. While IL-2 expands regulatory T cells and CD4+ helper T cells, IL-15 supports the development of central memory T cells and NK cells. Recent data have provided evidence that IL-2 and IL-15 differ in their ability to activate T and NK cells to resist various forms of immune suppression. The diverse roles of these two cytokines have on immune cells lead to critical therapeutic implications for cancer treatment. In this review, we discuss the distinct roles of IL-2 and IL-15 in activating various functions in T and NK cells with a particular focus on the signals that participate in the resistance of tumor-derived immune suppressive factors. Furthermore, we summarize current clinical applications of IL-2 and IL-15 in metastatic malignancies, either as monotherapy or in combination with other agents, and highlight the future trends for research on these cytokine-based immunotherapies.

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SOCS-mediated immunomodulation of natural killer cells

Cited by 25 publications

References 94 publications

JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation

JAK/STAT Cytokine Signaling at the Crossroad of NK Cell Development and Maturation

Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells

Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy

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