Fig. 1
From: Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies
This diagram provides a comprehensive illustration of the interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R) pathway within the tumor microenvironment, detailing its intrinsic role in tumor immunology. IL-2R, encompassing three distinct chains—IL-2Rα (CD25), IL-2Rβ (CD122), and γc (CD132)—comes in three unique forms formed by different combinations of these chains. The depicted schematic demonstrates how the IL-2/IL-2R pathway activates Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3) following their phosphorylation, thereby prompting the downstream signaling across multiple specialized pathways. Each of these pathways displays unique modulation within regulatory T cells (Treg cells), differing distinctly from effector T cells (Teff) or conventional T cells (Tconv). Notable components that demonstrate increased activity within Treg cells, in comparison to Teff or Tconv cells, include the signal transducer and activator of transcription 5 (STAT5) and phosphatase and tensin homolog (PTEN). On the other hand, the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal–related kinase (Erk) pathways show enhanced activity within Teff or Tconv cells. Additionally, other significant transcription factors and regulators like IL2-inducible T-cell kinase (ITK), inhibitors of nuclear factor-κB (IκB), Nuclear factor of activated T-cells (NFAT), Activator protein-1 (AP-1), the C-JUN protein—a signal-transducing transcription factor of the AP-1 family, and Protein c-Fos—a proto-oncogene that is the human homolog of the retroviral oncogene v-fos, are also engaged in the IL-2 and IL-2R signaling pathway. These components further modulate the intricate signaling dynamics within the Treg, Teff, and Tconv cells. The Suppressors of Cytokine Signaling1 (SOCS1), a critical regulator of cytokine signaling, is also implicated in this pathway and contributes to the complex interplay of signals within the tumor microenvironment. This detailed insight into the IL-2/IL-2R signaling pathway, along with the roles of the associated proteins, aims to facilitate an enhanced understanding of tumor immunology and could possibly pave the way for novel therapeutic strategies. The figure was created using the online tool https://biorender.com/