The role of interleukin-6 in malignant mesothelioma

Abstract

Malignant mesothelioma (MM) still remains a dismal disease with a median overall survival between 9-12 months. During the past decade since the introduction of the multi-folate antagonist, pemetrexed, there have been no significant advances in its systemic treatment, particularly with novel therapeutics that have exhibited varying degrees of success in other solid tumours. In recent years, the pleiotropic proinflammatory cytokine, interleukin-6 (IL-6) has emerged as a mediator of pivotal processes such as cell proliferation and chemoresistance within the mesothelioma tumour microenvironment in addition to clinical symptoms commonly witnessed in this disease. This manuscript provides a brief summary on the pathophysiology and clinical management of MM, followed by the role of IL-6 in its tumourigenesis and the rationale for utilising anti-IL-6 therapeutics alongside standard chemotherapy and targeted agents in an attempt to prolong survival.

Keywords: Interleukin-6 (IL-6); STAT3; chemoresistance; malignant mesothelioma (MM).

Figure 1

IL-6 signalling. (A) The classic mode of IL-6 signalling involves IL-6 complexing with membrane bound IL-6R. Trans-signalling is mediated via IL-6-sgp80 complexes. Both modes involve association with membrane bound gp130 to induce downstream signalling; (B) sgp130 abrogates both classic signalling and trans-signalling by preferentially binding to IL-6-sgp80 complexes.