Figure 2.

Recombinant IL-2 is designed to preferentially bind to IL2Rα or IL2Rβγ to avoid Tregs expansion, while stimulating CD4⁺, CD8⁺, and NK cells. Recombinant IL-21 also stimulates CD4⁺, CD8⁺, and NK cells as well as TFh cells, creating an auto-amplification loop. Some treatments inhibit Treg cells, MDSCs or TAM, to remove the immunosuppression they exert, while others indirectly promote anti-tumor immune response through immunogenic cell death. Radiotherapy is a double-edged sword, it directly kills tumor cells, but post-treatment it favors the recruitment of Tregs that highly express CTLA4, resulting in enhanced immune-suppression.