Tumor-related interleukins: old validated targets for new anti-cancer drug development

Setrerrahmane, Sarra; Xu, Hong‐Xi

doi:10.1186/s12943-017-0721-9

Cited by 198 publications

(143 citation statements)

References 193 publications

(164 reference statements)

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“…Stromal cells and platelets contribute to PMN formation by secretion of pro‐angiogenic and ECM‐remodeling factors, for example, the platelet ADP receptor P2Y12. P2Y12 recruits BMDC and increases extracellular fibronectin deposition in the lung PMN, thereby selectively promoting pulmonary metastasis …”

Section: Tumor Secreted Factorsmentioning

confidence: 99%

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

Raskov

Orhan

Salanti

et al. 2020

Intl Journal of Cancer

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The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and growth of residual cancer. Human and animal studies show that cancer surgery can increase survival, migration and proliferation of residual tumor cells. To secure the survival and growth of disseminated tumor cells, the formation of premetastatic niches in target organs involves a complex interplay between microenvironment, immune system, circulating tumor cells, as well as chemical mediators and exosomes secreted by the primary tumor. This review describes the current understanding of the early mechanisms of dissemination, as well as how surgery may facilitate disease progression.

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Section: Tumor Secreted Factorsmentioning

confidence: 99%

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

Raskov

Orhan

Salanti

et al. 2020

Intl Journal of Cancer

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“…On the contrary, anti-inflammatory ILs (IL-2, IL-12, IL-10, and others) frequently activate antitumor immunity, thus interfering with tumor growth. These demonstrations could offer a promising therapeutic approach [85]. Although many IL functions are already well known, others still remain to be better evaluated, while others are yet to be discovered; thus, the understanding of the basic biological mechanisms of this complex immune microenvironment and the recognition of the effector functions should be augmented and potentiated to effectively target and destroy breast cancer bone metastasis.…”

Section: Discussionmentioning

confidence: 99%

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Salamanna

Borsari

Contartese

et al. 2019

Cancers

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Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up-and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.An initial literature search found 905 references, of which 151 articles were recognized using the PubMed database, 481 articles were recognized using Scopus, and 273 articles were found in the Web of Science Core Collection. Subsequently, the resulting references were submitted to a public reference manager (Mendeley 1.17.11) to eliminate duplicate articles, obtaining 666 articles. From the 666 articles obtained, after exclusion, 116 full-text articles were evaluated, of which 67 met the inclusion criteria. The 560 studies excluded from this review were excluded because they were meeting reports, reviews, book chapters, and case reports, and/or because they reported IL roles in primary breast tumor, as well as in lung, liver, and pulmonary metastasis, leukemia, osteosarcoma, ovarian tumor, melanoma, prostate cancer, autoimmune arthritis related to breast cancer, and other pathological conditions; however, they did not reveal the favorable development of bone metastases from breast cancer. In addition, we excluded studies where IL profiling was derived from breast cancer metastatic patients that were not grouped/analyzed based on the site of metastasis, and where breast cancer bone metastases were evaluated, but no IL roles/functions were examined. Finally, we also eliminated studies where responses to specific therapy (not IL-based) for breast cancer bone metastasis were analyzed, studies that evaluated the contributions of the sensory signaling pathways to neuropathic pain induced by breast cancer bone metastases, and studies on chronic s...

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“…Most of these cells secrete cytokines that may play a key role in inhibiting or promoting tumor progression 35 . The proinflammatory cytokines IL-4 and IL-6, produced either by host immune cells or tumor cells themselves, are associated with tumor malignancy in patients and animal cancer models 36,37,38 . At the cutaneous level, keratinocytes secrete IL-6 in order to enhance T cell-mediated antitumor activity and therefore, high IL-6 levels are considered a marker for immune system upregulation 37,38 .…”

Section: Discussionmentioning

confidence: 99%

“…The proinflammatory cytokines IL-4 and IL-6, produced either by host immune cells or tumor cells themselves, are associated with tumor malignancy in patients and animal cancer models 36,37,38 . At the cutaneous level, keratinocytes secrete IL-6 in order to enhance T cell-mediated antitumor activity and therefore, high IL-6 levels are considered a marker for immune system upregulation 37,38 . IL-4 is the most important Th2 cytokine, and it is mainly produced by activated T cells, mast cells, basophils and eosinophils in order to regulate lymphocyte proliferation and survival 37 .…”

Section: Discussionmentioning

confidence: 99%

“…At the cutaneous level, keratinocytes secrete IL-6 in order to enhance T cell-mediated antitumor activity and therefore, high IL-6 levels are considered a marker for immune system upregulation 37,38 . IL-4 is the most important Th2 cytokine, and it is mainly produced by activated T cells, mast cells, basophils and eosinophils in order to regulate lymphocyte proliferation and survival 37 . Interestingly, elevated serum IL-6 was correlated with a poor prognosis in melanoma, while IL-4 is thought to promote the proliferation and survival of several cancer cells 39,40,41 .…”

Section: Discussionmentioning

confidence: 99%

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A new clinical tool to predict outcome in early-stage melanoma patients

Mancuso¹,

Lage²,

Rasero

et al. 2019

Preprint

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Short title: Prognostic serum signature in early-stage melanomaWe have developed a prognostic equation that considers the serum IL-4, GM-CSF and DCD levels, along with the Breslow thickness to accurately classify melanoma outcome in patients. In this sense, a rigorous follow-up is recommended for early-stage melanoma patients with a high Breslow thickness, high serum IL-4 levels and low GM-CSF and DCD levels at the time of diagnosis, given the elevated risk for these patients to develop metastasis during follow-up.3 AbstractAround 25% of early-stage melanoma patients eventually develop metastasis. Thus, we set out to define serological biomarkers that could be used along with clinical and histopathological features of the disease to predict these events. We previously demonstrated that in stage II melanoma patients, serum levels of dermcidin (DCD) were associated with metastatic progression. Based on the relevance of the immune response on the cancer progression and the recent association of DCD with local and systemic immune response against cancer cells, serum DCD was analyzed in a new cohort of patients along with IL-4, IL-6, IL-10, IL-17A, IFN TGF and GM-CSF. We included 448 melanoma patients, 323 of whom were diagnosed as stages I-II according to AJCC. Levels of selected cytokines were determined by ELISA and Luminex and obtained data were analyzed employing Machine Learning and Kaplan-Meier techniques to define an algorithm capable of accurately classifying early-stage melanoma patients with a high and low risk of developing metastasis. The results show that in early-stage melanoma patients, serum levels of the cytokines IL-4, GM-CSF and DCD together with the Breslow thickness are those that best predict melanoma metastasis. Moreover, resulting algorithm represents a new tool to discriminate subjects with good prognosis from those with high risk for a future metastasis.

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Tumor-related interleukins: old validated targets for new anti-cancer drug development

Cited by 198 publications

References 193 publications

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

A new clinical tool to predict outcome in early-stage melanoma patients

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