Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation

Figure 1 Pleiotropic mechanisms of interleukin-21 in antitumor immunity. IL-21: Interleukin-21; JAK: Janus kinase; STAT3: Signal transducer and activator of transcription 3; Treg: Regulatory T cell; IFN: Interferon; NK: Natural killer; NKG2D: Natural killer receptor group 2 member D; Klf2: Kruppel-like factor 2; CXCR6: C-X-C motif chemokine receptor 6; PI3K: Phosphatidylinositol 3-kinase; Akt: Protein kinase B; IgA: Immunoglobulin A; XBP1: X-box binding protein 1; IgG: Immunoglobulin G.

Figure 2 Strategic combination therapies of interleukin-21 for remodeling the tumor microenvironment. IL-21: Interleukin-21; ICIs: Immune checkpoint inhibitors; PD-1: Programmed cell death protein 1; CTLA-4: Cytotoxic T-lymphocyte antigen-4; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; IL-21R: Interleukin-21 receptor; TME: Tumor microenvironment; Tregs: Regulatory T cells; MDSCs: Myeloid-derived suppressor cells; CAR: Chimeric antigen receptor; ICR: Inverted cytokine receptor; STAT3: Signal transducer and activator of transcription 3; Th17: T helper 17 cell; OV: Oncolytic virus; NK: Natural killer; DC: Dendritic cell; GM-CSF: Granulocyte-macrophage colony-stimulating factor.