Cytokines are molecules that help cells communicate at short range. Often, a single cytokine is measured in patient tissues to understand whether immune cells are actively clearing a tumor. We can learn whether a therapy works, even before changes in tumor burden are found. However, measuring multiple different cytokines better reflects ongoing anti-tumor activity. That is especially true for T cell-based therapies, as these cells secrete different cytokines when they eliminate tumors or not. We also need to consider that a single cytokine can perform activities that can either suppress, or support tumor growth. Taken together, we can best describe the function of T cells in a (pre) clinical setting by a palette of cytokines working together to paint a picture of ongoing immune responses to tumor cells.

Cytokines are key molecules within the tumor microenvironment (TME) that can be used as biomarkers to predict the magnitude of anti-tumor immune responses. During immune monitoring, it has been customary to predict outcomes based on the abundance of a single cytokine, in particular IFN-γ or TGF-β, as a readout of ongoing anti-cancer immunity. However, individual cytokines within the TME can exhibit dual opposing roles. For example, both IFN-γ and TGF-β have been associated with pro- and anti-tumor functions. Moreover, cytokines originating from different cellular sources influence the crosstalk between CD4⁺ and CD8⁺ T cells, while the array of cytokines expressed by T cells is also instrumental in defining the mechanisms of action and efficacy of treatments. Thus, it becomes increasingly clear that a reliable readout of ongoing immunity within the TME will have to include more than the measurement of a single cytokine. This review focuses on defining a panel of cytokines that could help to reliably predict and analyze the outcomes of T cell-based anti-tumor therapies.