Interleukin-1β and Cancer

Rébé, Cédric; Ghiringhelli, François

doi:10.3390/cancers12071791

Cited by 169 publications

(120 citation statements)

References 245 publications

(291 reference statements)

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…In the context of cancer, the inflammasome-IL-1 axis can be perceived as a double-edged sword with both pro- and antitumorigenic properties, which is extensively summarized in a recent paper by Rébé and Ghiringhelli ( 273 ). There is ample evidence demonstrating that in many different types of cancer, including malignancies in skin, colon and lung, upregulated expression of IL-1β correlates with progression of disease.…”

Section: Translational Implicationsmentioning

confidence: 99%

“…Cancer cells can also drive the production of IL-1β in tumor-associated inflammatory macrophages, as such installing an environment where immune responses are dampened, for instance via IL-1β-mediated accumulation of myeloid-derived suppressor cells (MDSCs) that produce IL-10 and recruit pro-tumorigenic neutrophils. Besides this, IL-1β has been described a promotor of angiogenesis and cancer cell metastasis ( 273 ). Consequentially, clinical cancer research strongly focuses on antagonizing IL-1 activity in patients, which can be achieved by treatment with NLRP3 inflammasome inhibitors, recombinant IL-1Ra or monoclonal antibodies that neutralize IL-1β ( 273 – 275 ).…”

Section: Translational Implicationsmentioning

confidence: 99%

“…Besides this, IL-1β has been described a promotor of angiogenesis and cancer cell metastasis ( 273 ). Consequentially, clinical cancer research strongly focuses on antagonizing IL-1 activity in patients, which can be achieved by treatment with NLRP3 inflammasome inhibitors, recombinant IL-1Ra or monoclonal antibodies that neutralize IL-1β ( 273 – 275 ). The CANTOS (for “canakinumab anti-inflammatory thrombosis outcome study”) trial evaluated the effect of treatment with canakinumab, an anti-IL-1β neutralizing monoclonal IgG1 antibody, in patients with a history of myocardial infarction and high circulating levels of C-reactive protein (CRP).…”

Section: Translational Implicationsmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-1 as Innate Mediator of T Cell Immunity

2021

View full text Add to dashboard Cite

The three-signal paradigm tries to capture how the innate immune system instructs adaptive immune responses in three well-defined actions: (1) presentation of antigenic peptides in the context of MHC molecules, which allows for a specific T cell response; (2) T cell co-stimulation, which breaks T cell tolerance; and (3) secretion of polarizing cytokines in the priming environment, thereby specializing T cell immunity. The three-signal model provides an empirical framework for innate instruction of adaptive immunity, but mainly discusses STAT-dependent cytokines in T cell activation and differentiation, while the multi-faceted roles of type I IFNs and IL-1 cytokine superfamily members are often neglected. IL-1α and IL-1β are pro-inflammatory cytokines, produced following damage to the host (release of DAMPs) or upon innate recognition of PAMPs. IL-1 activity on both DCs and T cells can further shape the adaptive immune response with variable outcomes. IL-1 signaling in DCs promotes their ability to induce T cell activation, but also direct action of IL-1 on both CD4+ and CD8+ T cells, either alone or in synergy with prototypical polarizing cytokines, influences T cell differentiation under different conditions. The activities of IL-1 form a direct bridge between innate and adaptive immunity and could therefore be clinically translatable in the context of prophylactic and therapeutic strategies to empower the formation of T cell immunity. Understanding the modalities of IL-1 activity during T cell activation thus could hold major implications for rational development of the next generation of vaccine adjuvants.

show abstract

Section: Translational Implicationsmentioning

confidence: 99%

Section: Translational Implicationsmentioning

confidence: 99%

Section: Translational Implicationsmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-1 as Innate Mediator of T Cell Immunity

2021

View full text Add to dashboard Cite

show abstract

“…Furthermore, in 2003, Voronov et al reported on the proangiogenic functions of IL-1, with blockage leading to a reduction in tumor growth of murine melanoma and breast cancer models in vivo [ 9 , 10 ]. As mentioned, the pleiotropic functions of IL-1β in cancer immunity have recently and extensively been reviewed [ 5 , 11 , 12 , 13 , 14 , 15 , 16 ]. Thus, we will not further elaborate the underlying mechanisms, but focus on past and present clinical trials assessing the role of IL-1 blockade in the treatment of malignant disease.…”

Section: Therapeutic Targeting Of Il-1 In Cancermentioning

confidence: 99%

“…Rébé and Ghiringhelli recently published an extensive review about the pleiotropic functions of interleukin-1β in cancer [ 5 ]. While in general, most reports focus on the protumoral effects of IL-1β in cancer biology, the authors highlighted antitumoral functions of IL-1β as well, raising important considerations for future developments of IL-1 blocking strategies in cancer.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Strategies for Targeting IL-1 in Cancer

Gottschlich

Endres

Kobold

2021

Cancers

View full text Add to dashboard Cite

Since its discovery, interleukin-1 has been extensively studied in a wide range of medical fields. Besides carrying out vital physiological functions, it has been implicated with a pivotal role in the progression and spreading of different cancer entities. During the last years, several clinical trials have been conducted, shedding light on the role of IL-1 blocking agents for the treatment of cancer. Additionally, recent developments in the field of immuno-oncology have implicated IL-1-induced signaling cascades as a major driver of severe chimeric antigen receptor T cell-associated toxicities such as cytokine release syndrome and immune effector cell-associated neurotoxicity. In this review, we summarize current clinical trials investigating the role of IL-1 blockade in cancer treatment and elaborate the proposed mechanism of these innovative treatment approaches. Additionally, we highlight cutting-edge developments utilizing IL-1 blocking agents to enhance the safety and efficacy of adoptive T cell therapy.

show abstract

Neuropeptides in Cancer: Friend and Foe?

Berisha

Borniger

2022

Advanced Biology

View full text Add to dashboard Cite

highly dynamic network of various cell types (e.g., cancer cells, endothelial cells, immune cells, fibroblasts) that exert differential effects on neuronal activity within the local environment. Thus, complex signaling between cancer and stromal cells in the TME results in altered firing rates of local nerves. Reciprocally, increased neuronal activity and subsequent release of classical neurotransmitters and/or neuropeptides within the TME results in enhanced cancer progression and subsequent metastasis in various preclinical models and clinical studies. [5][6][7][8][9] Nerves interact with multiple stromal cells in the TME where they indirectly promote tumor growth, progression, and subsequent metastasis. [10] Several studies have demonstrated that sympathetic nerve innervation and subsequent release of the neurotransmitter norepinephrine (NE) is increased in breast tumors. [6,8,9] However, recent work has demonstrated that there is an inverse relationship between tumor weight and norepinephrine content (i.e., larger the size of the tumor, the lower the levels of NE), despite increased innervation of sympathetic nerves within the TME. [11] These findings may be attributed to a relatively unexplored phenomenon: neuropeptide release within the TME. Neuropeptides are molecular messengers that regulate a variety of functions in the central and peripheral nervous systems via binding G-protein-coupled receptors (GPCRs) on target cells. One of the many functions of neuropeptides is serving as growth factors for normal cells via the activation of the heterotrimeric G protein Gq and subsequent synthesis of second messengers and engagement of tyrosine phosphorylation cascades. Neuropeptides act as neuromodulators, in that they can alter the response of neurons to neurotransmitters and other circulating signals, such as leptin, ghrelin, glucose, and insulin-all of which are affected during cancer progression. [12][13][14][15][16][17] For example, both neuropeptide Y (NPY) and hypocretin/orexin neurons appear to mediate some of the orexigenic effects of centrally administered ghrelin as administration of NPY receptor antagonists attenuated ghrelininduced feeding. Similarly, ghrelin-induced feeding was suppressed in orexin knockout mice, indicating that ghrelin may stimulate feeding through both the orexin and NPY systems. [18] However, neuropeptide signaling is exploited within cancer cells and many studies demonstrate the contribution of neuropeptides in tumor cell proliferation and migration, [19] with many major neuropeptides also potentially contributing to cancer processes (see Table 1). Additionally, neuropeptides exert direct Neuropeptides are small regulatory molecules found throughout the body, most notably in the nervous, cardiovascular, and gastrointestinal systems. They serve as neurotransmitters or hormones in the regulation of diverse physiological processes. Cancer cells escape normal growth control mechanisms by altering their expression of growth factors, receptors, or intracellular signals, and neuropeptid...

show abstract

Interleukin-1β and Cancer

Cited by 169 publications

References 245 publications

Interleukin-1 as Innate Mediator of T Cell Immunity

Interleukin-1 as Innate Mediator of T Cell Immunity

Therapeutic Strategies for Targeting IL-1 in Cancer

Neuropeptides in Cancer: Friend and Foe?

Contact Info

Product

Resources

About