Something old, something new: The marriage of PD-1 and IL-2

IL-2 remains a promising candidate for immunotherapy of cancer, but its use is hampered by systemic toxicities. In this issue of Immunity, Tichet, Hanahan, and colleagues demonstrate that an IL-2 variant fused to an anti-PD-1 antibody overcomes these limitations to promote impressive tumor control. This approach may be a path to treat tumors that do not respond to anti-PD-1 monotherapy. IL-2 remains a promising candidate for immunotherapy of cancer, but its use is hampered by systemic toxicities. In this issue of Immunity, Tichet, Hanahan, and colleagues demonstrate that an IL-2 variant fused to an anti-PD-1 antibody overcomes these limitations to promote impressive tumor control. This approach may be a path to treat tumors that do not respond to anti-PD-1 monotherapy. Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophagesTichet et al.ImmunityJanuary 10, 2023In BriefMost cancer patients respond transiently to immunotherapy, highlighting the importance of understanding the mechanisms underlying resistance. Tichet et al. reveal that the immunocytokine PD1-IL2v combined with anti-PD-L1 synergize to enable anti-tumor immunity against immunotherapy-resistant tumors. PD1-IL2v promotes stem-like, tumor-reactive CD8+ T cell expansion and high endothelial venule formation, whereas anti-PD-L1 reprograms macrophages and tumor vasculature to antigen-presenting and pro-inflammatory phenotypes. Full-Text PDF Open Access