PD-1 signaling on T cells is the major pathway that limits T cell immunity, but the efficacy of
anti–PD-1 therapy has been limited to a small proportion of patients with advanced cancers.
We fortuitously observed that anti–PD-1 therapy depends on IL-2 signaling, which raises the
possibility that a lack of IL-2 limits anti–PD-1–induced effector T cell expansion. To
selectively deliver IL-2 to PD-1+ CD8+ tumor-infiltrating lymphocytes (TILs), we engineered
a low-affinity IL-2 paired with anti–PD-1 (PD-1–laIL-2), which reduced affinity to peripheral …

Background Increased levels of tumor-infiltrating lymphocytes (TILs) are associated with
improved survival in patients with cancer. Anti–PD-1/PD-L1–based cancer immunotherapies
have revolutionized the treatment of cancers, and TIL abundance can be used as a
prediction marker for immunotherapy responsiveness. Even though PD-1/PD-L1 blockade
can release the brake on the T cell response, T cells are not fully functional and are limitedly
expanded in the tumor. Most patients either fail to respond or develop adaptive resistance …