Cytokines: Can Cancer Get the Message?

Abstract

Cytokines are small molecular messengers that have profound effects on cancer development. Increasing evidence shows that cytokines are heavily involved in regulating both pro- and antitumor activities, such as immune activation and suppression, inflammation, cell damage, angiogenesis, cancer stem-cell-like cell maintenance, invasion, and metastasis. Cytokines are often required to drive these cancer-related processes and, therefore, represent an important research area for understanding cancer development and the potential identification of novel therapeutic targets. Interestingly, some cytokines are reported to be related to both pro- and anti-tumorigenicity, indicating that cytokines may play several complex roles relating to cancer pathogenesis. In this review, we discuss some major cancer-related processes and their relationship with several cytokines.

Keywords: angiogenesis; cytokines; inflammation; tumor microenvironment.

Figure 1

Macrophage polarization is highly regulated by cytokines. Generally, inflammatory cytokines promote M1-type macrophage functions that lead to enhanced Th1 activation, tumor killing, tissue damage, and antigen presentation. In contrast, anti-inflammatory cytokines induce macrophages to become more M2-like, leading to increased tumor-promoting and immunosuppressive responses, such as Th2 activation, angiogenesis, wound healing, and cell proliferation.

Figure 2

The TME is composed of a diverse group of cells, including cancer cells, CSCs, adipocytes, neutrophils, TAMs, CAFs, and lymphocytes. Various cytokines secreted by these cells enhance angiogenesis and overall tumor progression.

Figure 3

Several cytokines, cell types, and signaling pathways drive angiogenesis. Increased vasculature supports tumor growth and aggressiveness. Bevacizumab may be used to block VEGF, while TB-403 may potentially be used to inhibit PIGF to further prevent angiogenesis in TMEs.

Figure 4

CSCs and cytokines secreted by immune cells infiltrating the tumor promote EMT and invasive activity. Eventually, cancer cells may intravasate into local blood vessels to metastasize and colonize other tissues.