Immune mediators in the tumor microenvironment of prostate cancer

Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller, Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller

Abstract

Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor. Immune cells can have both anti-tumor and pro-tumor activity. In addition, crosstalk between prostate cancer cells and immune cells affects immune cell functions. In this review, we focus on immune cells and cytokines that contribute to tumor progression. We discuss T-regulatory and T helper 17 cells and macrophages as key modulators in prostate cancer progression. In addition, we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression. This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.

Keywords: Interleukin-6; Macrophage; Prostate cancer; Receptor activator of nuclear factor kappa-B ligand; T-regulatory cell; Th17 cell; Tumor microenvironment.

Figures

Fig. 1
Fig. 1
Key immune cells and cytokines in the tumor microenvironment of prostate cancer. Tregs suppress the activation of anti-tumor T cells to promote tumor progression. Th17 cells may promote or inhibit prostate cancer progression depending on the context. Macrophages promote prostate cancer growth through efferocytosis. Inflammatory stimuli can lead to IL-6 production, which, in turn, can promote prostate cancer growth. Prostate cancer cells can produce RANKL directly and stimulate host cells (e.g., osteocytes) to produce RANKL in the tumor microenvironment. RANKL can then mediate tumor-induced bone remodeling through osteoclast activation. IL-6 interleukin-6, Mɸ macrophage, RANKL receptor activator of nuclear factor kappa-B ligand, Th17 T helper 17, Treg T-regulatory cell, FoxP3 forkhead box P3

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