Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Gelfo, Valerio; Romaniello, Donatella; Mazzeschi, Martina; Sgarzi, Michela; Grilli, Giada; Morselli, Alessandra; Manzan, Beatrice; Rihawi, Karim; Lauriola, Mattia

doi:10.3390/ijms21176009

Cited by 122 publications

(90 citation statements)

References 92 publications

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“…Alongside these promising results, the safety analysis unraveled an increased risk of death for sepsis or infection in patients treated with canakinumab, especially for elderly and diabetic patients. By contrast, a reduced mortality for cancer was associated with the treatment [192], consistent with a large amount of experimental evidence supporting a role of the IL-1 cytokines superfamily in induction and progression of different cancer types [83]. However, all-cause mortality was not affected by the treatment with canakinumab.…”

Section: Interleukin 1 (Il-1)supporting

confidence: 70%

Cytokines as therapeutic targets for cardio- and cerebrovascular diseases

et al. 2021

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Despite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.

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Section: Interleukin 1 (Il-1)supporting

confidence: 70%

Cytokines as therapeutic targets for cardio- and cerebrovascular diseases

et al. 2021

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“…The combination with mAbs is a great focus of future development for IL-1-related therapies, both with immune checkpoint inhibitors, and with other molecularly targeted antibody classes of drugs. As tumor-hyperactivated IL-1 signaling is also responsible for the failure of targeted therapies, targeted therapies using monoclonal antibodies in combination with IL-1 blockade might have improved efficacy [145]. There are a number of recent studies that support this inference.…”

Section: Targeting Il-1 Signaling For Breastmentioning

confidence: 99%

Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling

Liu

Lan

et al. 2021

Mediators of Inflammation

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Breast cancer is one of the top-ranked cancers for incidence and mortality worldwide. The biggest challenges in breast cancer treatment are metastasis and drug resistance, for which work on molecular evaluation, mechanism studies, and screening of therapeutic targets is ongoing. Factors that lead to inflammatory infiltration and immune system suppression in the tumor microenvironment are potential therapeutic targets. Interleukin-1 is known as a proinflammatory and immunostimulatory cytokine, which plays important roles in inflammatory diseases. Recent studies have shown that interleukin-1 cytokines drive the formation and maintenance of an inflammatory/immunosuppressive microenvironment through complex intercellular signal crosstalk and tight intracellular signal transduction, which were found to be potentially involved in the mechanism of metastasis and drug resistance of breast cancer. Some preclinical and clinical treatments or interventions to block the interleukin-1/interleukin-1 receptor system and its up- and downstream signaling cascades have also been proven effective. This study provides an overview of IL-1-mediated signal communication in breast cancer and discusses the potential of IL-1 as a therapeutic target especially for metastatic breast cancer and combination therapy and current problems, aiming at enlightening new ideas in the study of inflammatory cytokines and immune networks in the tumor microenvironment.

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“…In MM, the cytokine network is involved in tumour growth, progression, and spread. It has also been shown that cytokines are involved in the destruction of the bone marrow, which is typically observed in the course of MM [ 10 , 11 ]. It has been reported that the documented activity of multiple cytokine subsets in MM patients, such as interleukins, tumour necrosis factors, growth factors, interferons, and chemokines, can serve as prognostic factors for the course of the disease.…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

“…It has also been reported that tumour cells can directly produce IL-1 in a positive feedback loop, contributing to the failure of targeted therapies. Overall, a high level of IL-1 is a factor that leads to poor prognosis in cancer patients [ 11 ]. Clinical studies (NCT00635154) have shown that IL-1 plays an important role in the conversion of the latent form of myeloma to the active form of MM [ 14 ].…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Immunological Prognostic Factors in Multiple Myeloma

Bębnowska

Hrynkiewicz

Grywalska

et al. 2021

IJMS

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Multiple myeloma (MM) is a plasma cell neoplasm characterized by an abnormal proliferation of clonal, terminally differentiated B lymphocytes. Current approaches for the treatment of MM focus on developing new diagnostic techniques; however, the search for prognostic markers is also crucial. This enables the classification of patients into risk groups and, thus, the selection of the most optimal treatment method. Particular attention should be paid to the possible use of immune factors, as the immune system plays a key role in the formation and course of MM. In this review, we focus on characterizing the components of the immune system that are of prognostic value in MM patients, in order to facilitate the development of new diagnostic and therapeutic directions.

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Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Cited by 122 publications

References 92 publications

Cytokines as therapeutic targets for cardio- and cerebrovascular diseases

Cytokines as therapeutic targets for cardio- and cerebrovascular diseases

Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling

Immunological Prognostic Factors in Multiple Myeloma

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