**11. Cytokines**

Neoplastic cells produce different cytokines that alter the tumor microenvironment. The tumor microenvironment has an extremely delicate balance between antitumor effects and the origin of tumors arising from pro-inflammatory activity that is dependent on the mediator cells [36]. Therefore, the cytokines may have antitumor and protumor effects, depending on the interrelationship between the



#### **Table 1.**

*Main cytokines relevant to tumor immunotherapy.*

tumor and constituents of the tumor microenvironment [37]. Thus, the use of cytokines as therapeutic agents is quite complex, as their action is dependent on the status acquired in the tumor microenvironment. Lin and Karin [37] also showed that chronic inflammation leads to the production of several cytokines that allow tumor development, highlighting that the interaction between cells present in the tumor microenvironment determines the effects of the released cytokines. Catchpole et al. [38], for example, demonstrated an increase in the production of IL-10 and TGF-β and a decrease in that of IL-2, IL-4, and IFN-γ in the lymph nodes with melanoma metastasis. Each cytokine has different actions on different cells, and its effects can either help in carcinogenesis or confer antitumor activity (**Table 1**).
