Samuel Evans Adunyah

By Chantel F. Faqua, Richard Akomeah and Samuel Evans Adunyah

Interleukin-21 (IL-21) is produced by activated T cells and it plays many diverse roles by regulating the functions of normal and abnormal cells. Its roles include regulation of proliferation, promotion of immune system and activation of apoptosis in B cells. IL-21R is a type-1 cytokine receptor and belongs to the IL-2R and IL-15R family. The signaling mechanisms of IL-21 in different cell types have been identified. However, we know less about the biological effects of IL-21 and its signaling mechanisms in leukemia cells and monocytes. In this chapter, we will focus on IL-21’s biological effects and signaling pathways as well as discuss the potential implications and applications of IL-21 in leukemia cells. In these cells, IL-21 does not promote proliferation but enhances apoptosis and chemotaxis. Furthermore, IL-21 promotes differential expression of many cytokines including interleukins and chemokines. IL-21 activates both the Raf-ERK-MAPK and the Jak/STAT signaling pathways. These pathways mediate some of the effects of IL-21. Lastly, IL-21 also promotes activation of the STAT3 promoter and other transcriptional factors. These findings may be relevant to IL-21’s potential clinical implications and applications.

Part of the book: Cytokines

By Samuel Evans Adunyah, Richard Akomeah, Fareed K.N. Arthur, Roland S. Cooper and Joshua C.M. Williams

Human Interlekin-17 is produced by memory activated CD4+ T cells and other cells. It was initially considered unique in that its specific receptor is distinct from other cytokine receptors. IL-17 receptor is ubiquitously expressed by different cells including T cells. IL-17 plays a role in regulating growth, immune response and pro-inflammatory responses. It regulates differentiation of a subset of Th0 cells into Th-17 cells, which produce IL-17-induced cytokines. The IL-17R belongs to type 1 cytokine receptors. IL-17 belongs to a superfamily of its own, which includes IL-17A, IL-17B, IL-17C, IL-17E and IL-17F. These members of IL-17 superfamily have some sequence homology but bind to different receptors. Prior to this investigation, limited information existed on the effects of IL-17A in human leukemia cell lines. Our results show that IL-17A promotes growth, anti-apoptotic effects, chemotaxis, cytokine expression and transcriptional factor activation in leukemia cells. IL-17A activates multiple signaling pathways including PI-3 K, Jak–STAT, Raf-ERK1/2 and SRC kinase pathways, which mediate different biological effects of IL-17A in leukemia cells. Our findings implicate IL-17A in leukemia cell growth and survival, supporting potential leukemia therapy via development of anti-IL-17A drugs. This chapter focuses on IL-17A, herein referred to as IL-17.

Part of the book: Interleukins

By Deok-Soo Son and Samuel Evans Adunyah

Chemokines regulate cell migration by binding to specific cell surface G protein-coupled receptors in development, physiology, and immune responses. Particularly in cancer, chemokines are involved in tumor cell growth, angiogenesis, cancer stem-like cell properties, metastasis, and directly and indirectly influencing tumor immunity and cancer progression. The chemokine signature in the tumor microenvironment affects immune contexture in tumor tissues and mutual communication between cells through the specific chemokine axis, contributing to cancer prognosis. The present chapter summarizes the role of chemokines in the tumor microenvironment in breast cancer, of which subtypes are classified as luminal A, luminal B, HER2-enriched, and basal-like, focusing on expression levels of chemokines and overall survivals in a chemokine-dependent manner and discovering the target chemokine axis. The outcome provides valuable information that improves the quality of life in patients with breast cancer by supporting the treatment options via the chemokine network in the tumor microenvironment.

Part of the book: New Updates in Tumor Microenvironment

By Samuel Evans Adunyah

Part of the book: New Updates in Tumor Microenvironment