New perspectives in cancer immunotherapy: targeting IL-6 cytokine family

Abstract

Chronic inflammation has been recognized as a canonical cancer hallmark. It is orchestrated by cytokines, which are master regulators of the tumor microenvironment (TME) as they represent the main communication bridge between cancer cells, the tumor stroma, and the immune system. Interleukin (IL)-6 represents a keystone cytokine in the link between inflammation and cancer. Many cytokines from the IL-6 family, which includes IL-6, oncostatin M, leukemia inhibitory factor, IL-11, IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin 1, and cardiotrophin-like cytokine factor 1, have been shown to elicit tumor-promoting roles by modulating the TME, making them attractive therapeutic targets for cancer treatment.The development of immune checkpoint blockade (ICB) immunotherapies has radically changed the outcome of some cancers including melanoma, lung, and renal, although not without hurdles. However, ICB shows limited efficacy in other solid tumors. Recent reports support that chronic inflammation and IL-6 cytokine signaling are involved in resistance to immunotherapy. This review summarizes the available preclinical and clinical data regarding the implication of IL-6-related cytokines in regulating the immune TME and the response to ICB. Moreover, the potential clinical benefit of combining ICB with therapies targeting IL-6 cytokine members for cancer treatment is discussed.

Tocilizumab in the treatment of steroid refractory immune-related hepatotoxicity: a case series and review of the literature

“…In addition, high levels of IL-6 are thought to contribute to tumor cell survival and growth and thus cancer progression [25,29]. In preclinical models, the addition of tocilizumab to ICIs has been shown to contribute to antitumor activity [30]. This gives us a reason to prioritize tocilizumab, as it can treat IRH without causing cancer progression.…”

Navigating the Cytokine Seas: Targeting Cytokine Signaling Pathways in Cancer Therapy

“…Soler et al also reviewed the up-to-date data on preclinical and clinical trials targeting the IL-6 cytokine family in cancer, including IL-6, oncostatin M, leukemia inhibitory factor, IL-11, IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin 1, and cardiotrophin-like cytokine factor 1 [113].…”

“…Recently, the need for predictive biomarkers to assess cytokine-based immunotherapy for cancer has led to robust investigations designed to find rational therapeutic strategies and suitable targets. This is especially valid since cytokines typically function in loops and collaborate with other cytokines and chemokines, and targeting many cytokines at once may occasionally provide more effective antitumor effects than utilizing cytokine-targeting medications in monotherapy [113].…”

Mitochondrial Signatures Shape Phenotype Switching and Apoptosis in Response to PLK1 and RSK Inhibitors in Melanoma

“…The copyright holder for this preprint this version posted June 17, 2024. ; https://doi.org/10.1101/2024.06.14.599035 doi: bioRxiv preprint was among the most enriched up-regulated transcripts from the Inflammatory Response gene set (Figure 2G), we next asked whether the corresponding cytokine IL-8 was secreted by MeWo after treatment with BI-D1870. The analysis of cytokines from conditioned media of MeWo revealed a 7-fold induction in IL-8 (Figure 2H and 2I) as well as significant induction of other cytokines associated with melanoma progression and therapeutic resistance, such as GROa (CXCL1) 28,29 and IL-6 30 (Figure S2D and S2E).…”