Molecular cross‐talk of IL‐6 in tumors and new progress in combined therapy

Abstract

IL‐6, a cytokine activated by type I interferons (IFNs), is encoded by the IL‐6 gene, and secreted by T cells and macrophages. It serves many purposes in the human body and is significant to pathological and physiological activities, such as acute inflammatory responses, autoimmune diseases, and tumor formation. The wide range of IL‐6 actions on tumors rely on more than one specific pathway. Advances in modern research have determined that to fulfill its complex physiological functions, IL‐6 must be involved in cross‐talk with a number of other molecular pathways. Therefore, it is important to clarify the comprehensive pathway network associated with IL‐6 activity and to explore the mechanisms to inhibit its pathological activity in order to develop corresponding treatment plans. This study is a simple review of the pathological and physiological actions of IL‐6 on the human body. It explains in detail the molecular pathways involved in cross‐talk between IL‐6 and tumors, summarizing and discussing the latest progress made in IL‐6‐related internal medicine treatments in recent years, including chemotherapies, targeted therapies, and immunotherapies. Our results provide new insight into the treatment of tumors.

Biological characteristics of IL-6 and related intestinal diseases

“…this axis exerts both inter-cellular and extra-cellular pro-tumor effects, coinciding with the results of previous clinical cases that increasing level of IL-6 in CRC patients indicates high mortality and bad prognosis [126,127].…”

“…Working mainly via the trans-signaling pathway in the regulation of TGF-β 124 , IL-6/JAK/STAT3 signaling axis is at the core of regulating many gene transcription and expression that play crucial roles in the generation and development of tumor 125 . And this axis exerts both inter-cellular and extra-cellular pro-tumor effects, coinciding with the results of previous clinical cases that increasing level of IL-6 in CRC patients indicates high mortality and bad prognosis 126 , 127 .…”

Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles

“…IL-6 is mainly produced by macrophages, T lymphocytes, B lymphocytes, monocytes, and so on [125]. IL-6 is a multifunctional cytokine that promotes tumor cell proliferation, invasion, and metastasis; inhibits tumor cell apoptosis; and promotes blood vessel growth [126]. IL-6 mainly relies on the activation of multiple signaling pathways to participate in the development of tumors, such as the JAK2/STAT3 signaling pathway, PI3K/AKT signaling pathway, RAS/MAPK signaling pathway, and so on [127].…”

Mechanistic insight into the gut microbiome and its interaction with host immunity and inflammation

“…Then, TLR4 combines with MyD88 and activates IL-1 receptor related kinase, tumor necrosis factor receptor associated factor 6, NF-κB inhibitor kinase, and NF-κB to up-regulate the expression levels of TNF-α , IL-6 , and IL-1 ( Yang et al., 2016 ). IL-6 is secreted by macrophages, T cells, B cells, and mesenchymal cells ( Song et al., 2018 ). Before playing the biological role, IL-6 combines with IL-6 binding receptor protein and glycoproteins 30.…”