A forced marriage of IL-2 and PD-1 antibody nurtures tumor-infiltrating T cells

IL-2 is a pleiotropic cytokine. In this issue of the JCI, Ren et al. report on the development of a low-affinity IL-2 paired with anti–PD-1 (PD-1–laIL-2) that reactivates intratumoral CD8(+) T cells, but not CD4(+) Treg cells. PD-1–laIL-2 treatment synergized with anti–PD-L1 therapy to overcome tumor resistance to immune checkpoint blockade (ICB) in tumor-bearing mice. Rejection of rechallenged tumors following PD-1–laIL-2 therapy demonstrated the establishment of a potent T cell memory response. Furthermore, PD-1–laIL-2 therapy manifested no obvious toxicity. These findings suggest the potential of PD-1–laIL-2 therapy in treating patients with cancer.