IL-12 initiates tumor rejection via lymphoid tissue–inducer cells bearing the natural cytotoxicity receptor NKp46

Eisenring, Maya; Berg, Johannes vom; Kristiansen, Glen; Saller, Elisabeth; Becher, Burkhard

doi:10.1038/ni.1947

Cited by 197 publications

(185 citation statements)

References 47 publications

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“…However, the functions of ILC in the presence of adaptive immunity and their potential to influence adaptive immune cell responses against cancers in inflammation context remain poorly understood. IL-12-activated NCR + ILC3 has been described to initiate antitumor immunity by upregulation of adhesion molecules in the tumor vasculature, which resulted in more leukocyte invasion (49). Conversely, ILC3, which expresses CCR6 and produces IL-22, was shown to tumorigenic potential (50,51).…”

Section: Discussionmentioning

confidence: 99%

IL-21–Induced MHC Class II+ NK Cells Promote the Expansion of Human Uncommitted CD4+ Central Memory T Cells in a Macrophage Migration Inhibitory Factor–Dependent Manner

Loyon

Picard

Mauvais

et al. 2016

The Journal of Immunology

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NK cells are critical for innate immunity–mediated protection. The main roles of NK cells rely on their cytotoxic functions or depend on the tuning of Th1 adaptive immunity by IFN-γ. However, the precise influence of inflammatory cytokines on NK cell and CD4 T lymphocyte interactions was never investigated. In this study, we provide evidence that IL-21, a cytokine produced during chronic inflammation or infectious diseases, promotes the differentiation of a specific subset of NK cells coexpressing CD86 and HLA-DR and lacking NKp44. More importantly, IL-21–propagated HLA-DR+ NK cells produce macrophage migration inhibitory factor and provide costimulatory signaling during naive CD4+ T cell priming inducing the differentiation of uncommitted central memory T cells. Central memory T cells expanded in the presence of HLA-DR+ NK cells are CXCR3+CCR6−CCR4−CXCR5− and produce IL-2, as well as low levels of TNF-α. Costimulation of CD4+ T cells by HLA-DR+ NK cells prevents the acquisition of effector memory phenotype induced by IL-2. Moreover, we identified this population of NK HLA-DR+ macrophage migration inhibitory factor+ cells in inflammatory human appendix. Collectively, these results demonstrate a novel function for IL-21 in tuning NK and CD4+ T cell interactions promoting a specific expansion of central memory lymphocytes.

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Section: Discussionmentioning

confidence: 99%

IL-21–Induced MHC Class II+ NK Cells Promote the Expansion of Human Uncommitted CD4+ Central Memory T Cells in a Macrophage Migration Inhibitory Factor–Dependent Manner

Loyon

Picard

Mauvais

et al. 2016

The Journal of Immunology

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“…The overexpression of IL-12 in B16 melanoma, thricostatin-A (TSA) mammary adenocarcinoma and C26 colon carcinoma cells induced tumor suppression upon subcutaneous (s.c.) inoculation. [43][44][45][46] Whereas in B16 melanoma this effect was mediated by a subset of innate lymphoid cells (ILCs), the By using mice lacking IL-23, IL-23 receptor or anti-IL23p19 blocking antibodies, endogenous IL-23 was shown to promote tumor growth in different tumor models. 142,143 In colorectal carcinoma, the effects of IL-23 were mimicked after blocking IL-17A.…”

Section: Mechanisms Of Tumor Protection Through Il-12mentioning

confidence: 99%

“…Hence, overexpression of IL-12 in B16 melanoma tumors was shown to regulate the tumor vasculature, either by upregulating of adhesion molecules that may facilitate leukocyte recruitment 44 or by inhibiting angiogenesis in an IFNg-dependent manner. 49,50 The inhibitory effects of IL-12 on the tumor vessels have been associated with increased levels of the IFNg-inducible chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL10, and a decreased production of vascular endothelial growth factor (VEGF) and metalloproteinase-9.…”

Section: Mechanisms Of Tumor Protection Through Il-12mentioning

confidence: 99%

New insights into IL-12-mediated tumor suppression

et al. 2014

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During the past two decades, interleukin-12 (IL-12) has emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models. Through pleiotropic effects on different immune cells that form the tumor microenvironment, IL-12 establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines depending on the type of tumor or the affected tissue. The robust antitumor response exerted by IL-12, however, has not yet been successfully translated into the clinics. The majority of clinical trials involving treatment with IL-12 failed to show sustained antitumor responses and were associated to toxic side effects. Here we discuss the therapeutic effects of IL-12 from preclinical to clinical studies, and will highlight promising strategies to take advantage of the antitumor activity of IL-12 while limiting adverse effects.

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“…99 In a mouse model of melanoma, ILCs promote tumor rejection. 100 Studies are required to understand the role of ILC subsets in TCs.…”

Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning

confidence: 99%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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IL-12 initiates tumor rejection via lymphoid tissue–inducer cells bearing the natural cytotoxicity receptor NKp46

Cited by 197 publications

References 47 publications

IL-21–Induced MHC Class II+ NK Cells Promote the Expansion of Human Uncommitted CD4+ Central Memory T Cells in a Macrophage Migration Inhibitory Factor–Dependent Manner

IL-21–Induced MHC Class II+ NK Cells Promote the Expansion of Human Uncommitted CD4+ Central Memory T Cells in a Macrophage Migration Inhibitory Factor–Dependent Manner

New insights into IL-12-mediated tumor suppression

The immune network in thyroid cancer

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