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

ABSTRACT

Introduction: 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.

KEYWORDS:

• IL-23
• IL-17
• Th17
• non-small cell lung cancer

Article highlights

• The IL-17/Th17 pathway may be a critical therapeutic avenue of interest in NSCLC.

• Significant evidence points to an aberrant IL-23 signaling pathway in NSCLC.

• anti-IL-23 targeting agents are under development for the treatment of Ps and other autoimmune indications. Such therapies could conceivably be re-purposed for use in lung cancer.

• Additional agents such as PDE-4 inhibitors, JAK/STAT inhibitors have also been shown to affect the IL-17/Th17 signaling pathway and may also have similar potential for use in lung cancer.

• The long-term safety profiles and efficacy of the agents under development suggest that targeting this pathway may have significant therapeutic potential in lung cancer.

• New evidence suggests that the IL-17/Th17 and PD-1 pathways may be linked raising the possibility that combined anti-PD(L)1/anti-IL-17 or anti-PD(L)1/anti-IL23 targeting may be synergistic.

This box summarizes key points contained in the article.

Declaration of interest

M Joerger and SG Gray declare materials provided by Novartis. SG Gray declares materials provided by Jannsen-Cilag. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.