IL-27 Enhances Anti-Tumor Immunity by Promoting CD8+ T Cell Persistence and Effector Function

Although immune checkpoint therapy has shown significant efficacy in various cancer types, most patients still do not respond to the treatment, highlighting the need to develop alternative or complementary therapeutic strategies. The dysfunction of cytotoxic T lymphocytes (CTLs) may be one of the critical factors severely limiting the efficacy of immunotherapy. Currently, cytokines have been extensively studied as potential therapeutic agents due to their effective role in T-cell survival and function. However, the clinical application of cytokines is restricted by their immune-related toxicity and rapid clearance in vivo. Therefore, identifying cytokines with antitumor activity and favorable safety profiles has become an important challenge in the field of cancer immunotherapy.

In February 2025, Nathaniel R. West's team at Genentech published a research paper titled "IL-27 elicits a cytotoxic CD8+ T cell program to enforce tumour control" in the journal *Nature*. The study explored the crucial role of the cytokine IL-27 in anti-tumor immunity, showing that IL-27 directly acts on tumor-specific CTLs, promoting their persistence and effector function within the tumor microenvironment. Agonistic action of the IL-27 receptor can safely enhance anti-tumor T-cell responses when used alone with PD-L1 blockade or in combination (*Nature*. 2025 Mar;639(8055):746-753. doi: 10.1038/s41586-024-08510-w).