IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells

Choi, Yujung; Lim, Eic Ju; Kim, Se Wha; Moon, Yong Wha; Park, Kyung Soon; An, Hee-Jung

doi:10.1186/s40425-019-0652-7

Cited by 75 publications

(58 citation statements)

References 47 publications

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“…In addition, use of IL-27 may enhance cytokine-mediated toxicity of NK cells. For example, the use of IL-15 can enhance NK cell cytotoxic function against ovarian cancer (167, 168) and IL-27 has been shown to enhance IL-15 mediated NK cell activation (169). This suggests that IL-27 should be further explored for use in combination with other cytokines to improve cytotoxic immune cell therapies.…”

Section: Il-27 Il-30 and Il-35: Influencing Cancer Developmentmentioning

confidence: 99%

IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer

et al. 2019

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The role of the immune system in anti-tumor immunity cannot be overstated, as it holds the potential to promote tumor eradication or prevent tumor cell escape. Cytokines are critical to influencing the immune responses and interactions with non-immune cells. Recently, the IL-12 and IL-6 family of cytokines have accumulated newly defined members each with specific immune functions related to various cancers and tumorigenesis. There is a need to better understand how cytokines like IL-27, IL-30, and IL-35 interact with one another, and how a developing tumor can exploit these interactions to enhance immune suppression. Current cytokine-based immunotherapies are associated with cytotoxic side effects which limits the success of treatment. In addition to this toxicity, understanding the complex interactions between immune and cancer cells may be one of the greatest challenges to developing a successful immunotherapy. In this review, we bring forth IL-27, IL-30, and IL-35, “sister cytokines,” along with more recent additions to the IL-12 family, which serve distinct purposes despite sharing structural similarities. We highlight how these cytokines function in the tumor microenvironment by examining their direct effects on cancer cells as well their indirect actions via regulatory functions of immune cells that act to either instigate or inhibit tumor progression. Understanding the context dependent immunomodulatory outcomes of these sister cytokines, as well as their regulation within the tumor microenvironment, may shed light onto novel cancer therapeutic treatments or targets.

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Section: Il-27 Il-30 and Il-35: Influencing Cancer Developmentmentioning

confidence: 99%

IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer

et al. 2019

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“…For example, signaling through WSX-1 and gp130 on CD8 + T cells activated STAT1 and STAT4 and resulted in the increased expression of granzyme, perforin and IFN-γ in a T-bet-dependent manner [ 128 , 129 ]. In NK cells, the activation of STAT1/STAT4 by IL-27 stimulated T-bet-dependent IFN-γ production and IL-27R expression [ 130 , 131 ]. These overall pro-inflammatory effects of IL-27 can stimulate anti-tumor immunity and contribute to tumor cell clearance [ 130 , 131 , 132 ].…”

Section: Introduction Il-12 Family Cytokines: Composition Signalmentioning

confidence: 99%

IL-12 Family Cytokines in Cancer and Immunotherapy

Mirlekar

Pylayeva-Gupta

2021

Cancers

153

102

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The IL-12 family cytokines are a group of unique heterodimeric cytokines that include IL-12, IL-23, IL-27, IL-35 and, most recently, IL-39. Recent studies have solidified the importance of IL-12 cytokines in shaping innate and adaptive immune responses in cancer and identified multipronged roles for distinct IL-12 family members, ranging from effector to regulatory immune functions. These cytokines could serve as promising candidates for the development of immunomodulatory therapeutic approaches. Overall, IL-12 can be considered an effector cytokine and has been found to engage anti-tumor immunity by activating the effector Th1 response, which is required for the activation of cytotoxic T and NK cells and tumor clearance. IL-23 and IL-27 play dual roles in tumor immunity, as they can both activate effector immune responses and promote tumor growth by favoring immune suppression. IL-35 is a potent regulatory cytokine and plays a largely pro-tumorigenic role by inhibiting effector T cells. In this review, we summarize the recent findings on IL-12 family cytokines in the control of tumor growth with an emphasis primarily on immune regulation. We underscore the clinical implications for the use of these cytokines either in the setting of monotherapy or in combination with other conventional therapies for the more effective treatment of malignancies.

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“…Additional studies have demonstrated that NK cells mediate protective responses to MTB through their interactions with CD8 + T cells ( 66 ) and γδ T cells ( 67 ), and by directly engaging with infected macrophages ( 68 , 69 ). NK cell effector functions are associated with IL15, IL18, IL27 ( 70 , 71 ), and, specifically in the context of MTB infection, with IL21 ( 65 ), IL12 ( 72 ), TNFA ( 72 , 73 ) and IL22 ( 70 ). Vaccine-induced cytokine responses in the CPP of Silirum vaccinates reflected similar cytokine responses ( IL12 , IL21 , IL27 and TNFA ) that have previously been associated with NK cell activity.…”

Section: Discussionmentioning

confidence: 99%

A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery

et al. 2020

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Mycobacterial diseases of cattle are responsible for considerable production losses worldwide. In addition to their importance in animals, these infections offer a nuanced approach to understanding persistent mycobacterial infection in native host species. Mycobacteriumavium ssp. paratuberculosis (MAP) is an enteric pathogen that establishes a persistent, asymptomatic infection in the small intestine. Difficulty in reproducing infection in surrogate animal models and limited understanding of mucosal immune responses that control enteric infection in the natural host have been major barriers to MAP vaccine development. We previously developed a reproducible challenge model to establish a consistent MAP infection using surgically isolated intestinal segments prepared in neonatal calves. In the current study, we evaluated whether intestinal segments could be used to screen parenteral vaccines that alter mucosal immune responses to MAP infection. Using Silirum® – a commercial MAP bacterin – we demonstrate that intestinal segments provide a platform for assessing vaccine efficacy within a relatively rapid period of 28 days post-infection. Significant differences between vaccinates and non-vaccinates could be detected using quantitative metrics including bacterial burden in intestinal tissue, MAP shedding into the intestinal lumen, and vaccine-induced mucosal immune responses. Comparing vaccine-induced responses in mucosal leukocytes isolated from the site of enteric infection versus blood leukocytes revealed substantial inconsistences between these immune compartments. Moreover, parenteral vaccination with Silirum did not induce equal levels of protection throughout the small intestine. Significant control of MAP infection was observed in the continuous but not the discrete Peyer’s patches. Analysis of these regional mucosal immune responses revealed novel correlates of immune protection associated with reduced infection that included an increased frequency of CD335+ innate lymphoid cells, and increased expression of IL21 and IL27. Thus, intestinal segments provide a novel model to accelerate vaccine screening and discovery by testing vaccines directly in the natural host and provides a unique opportunity to interrogate mucosal immune responses to mycobacterial infections.

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IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells

Cited by 75 publications

References 47 publications

IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer

IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer

IL-12 Family Cytokines in Cancer and Immunotherapy

A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery

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