IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Baird, Anne‐Marie; Leonard, Jennifer; Naicker, Krisha M.; Kilmartin, Lisa; O’Byrne, Kenneth J.; Gray, Steven G.

doi:10.1016/j.lungcan.2012.10.003

Cited by 36 publications

(33 citation statements)

References 48 publications

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“…However, in the current in vitro study, IL-23p40 was not produced. By contrast, Baird et al (48) confirmed the presence of IL-23 in the tumor microenvironment and demonstrated that IL-23 induced proliferation in an NSCLC cell line and promoted proliferation in primary NSCLC tumors (48). In the present study, a higher prevalence of IL-12/23p40 positive cells in lymph nodes and in tumor tissue was observed.…”

Section: Peripheral Blood Lymph Nodes Tumor Tissue ------------------contrasting

confidence: 64%

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Monocytic myeloid-derived suppressor cells as a potent suppressor of tumor immunity in non-small cell lung cancer

et al. 2016

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Abstract.Immunotherapy is a promising therapeutic option for patients with non-small cell lung cancer (NSCLC) who do not qualify for surgery. In patients with advanced NSCLC, systemic immune suppression is frequently observed, therefore, researchers are investigating the tumor microenvironment for less invasive and more effective methods of treating lung cancer. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are potent suppressors of tumor immunity; therefore, this population may significantly impede the application of immunotherapy to treat cancer. The present study evaluated the distribution of Mo-MDSCs and monocytes/macrophages in the peripheral blood, lymph nodes and tumor tissue of patients with NSCLC. Furthermore, the profiles of cytokines produced by these cell populations, including interleukin (IL)-1β, IL-12/23p40, IL-10, transforming growth factor-β (TGF-β) and tumor necrosis factor (TNF), were compared. The cell populations and the expression of cytokines were assessed by flow cytometry after 4 h in culture with mitogens and Brefeldin A. Mo-MDSCs were more numerous than monocytes/macrophages in all tissues and their prevalence was highest in the peripheral blood; they expressed higher levels of TGF-β than monocytes/macrophages in all

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Section: Peripheral Blood Lymph Nodes Tumor Tissue ------------------contrasting

confidence: 64%

“…In the present study, a higher prevalence of IL-12/23p40 positive cells in lymph nodes and in tumor tissue was observed. This may be associated with a more aggressive tumor, when the results of Baird et al (48) are considered.…”

Section: Peripheral Blood Lymph Nodes Tumor Tissue ------------------mentioning

confidence: 97%

Monocytic myeloid-derived suppressor cells as a potent suppressor of tumor immunity in non-small cell lung cancer

et al. 2016

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“…In a similar vein, we showed that IL-23R is expressed and epigenetically regulated in preclinical NSCLC models through histone post-translation modifications and CpG island methylation [29]. Furthermore, we also demonstrated that IL-23 itself is epigentically regulated and aberrantly expressed in NSCLC [29].…”

Section: Aberrant Epigenetics Of Critical Th17 Cytokines In Lung Cancersupporting

confidence: 60%

“…In support of the latter, increased Th17 infiltration in ovarian cancer has been associated with improved survival [28]. IL-23 has been shown to be pro-proliferative and associated with a more aggressive lung cancer phenotype [29]. Additionally, IL-23R overexpression has been demonstrated in ovarian cancer [30], NSCLC [31] and in colorectal cancer [32,33].…”

Section: Areas Coveredmentioning

confidence: 94%

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The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

Joerger

Finn

Cuffe

et al. 2016

Expert Opinion on Therapeutic Targets

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There is strong pharmaceutical development of agents targeting the IL-17-TH17 pathway for the treatment of psoriasis (Ps) and psoriatic arthritis (PsA). Lung cancer accounts for 28% of all cancer-related deaths worldwide, and roughly 80% of patients with newly-diagnosed non-small cell lung cancer (NSCLC) present with metastatic disease, with a poor prognosis of around 12 months. Therefore, there is a high unmet medical need for the development of new and potent systemic treatments in this deadly disease. The emergence of immunotherapies such as anti-PD-1 or anti-PDL1 as candidate therapies in non-small cell lung cancer (NSCLC) indicates that targeting critical immuno-modulatory cytokines including those within the IL-17-Th1/Th17 axis may have proven benefit in the treatment of lung cancer. Areas covered: In this review we describe the current evidence for aberrant IL-17-Th1/Th17 settings in cancer, particularly with regard to targeting this axis in NSCLC. We further discuss the current agents under pharmaceutical development which could potentially target this axis, and discuss the current limitations and areas of concern regarding the use of these in lung cancer. Expert opinion: Current evidence suggests that moving forward agents targeting the IL-17-Th1/Th17 pathway may have novel new oncoimmunology indications in the treatment paradigm for NSCLC.

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Tidrakizumab

Han

2020

Advances in Psoriasis

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IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Cited by 36 publications

References 48 publications

Monocytic myeloid-derived suppressor cells as a potent suppressor of tumor immunity in non-small cell lung cancer

Monocytic myeloid-derived suppressor cells as a potent suppressor of tumor immunity in non-small cell lung cancer

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

Tidrakizumab

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