Year: 2026
Type: conference-abstract
Abstract: Background Cytokines are essential modulators of anti-tumour immunity, but their utility as therapeutic agents has been limited by several challenges, including pleiotropic biology and poor tolerability. Our previous work uncovered a potential role for IL-27 in cancer immunotherapy. IL-27 acts directly on tumour-specific CD8 T cells to promote their persistence and effector function in the tumour microenvironment. Moreover, treatment with inducible IL-27 overexpression or a half-life-extended IL-27 protein in vivo is well tolerated, induces regression of established tumours, drives an enhanced cytotoxic program in anti-tumour CTLs, and synergizes with PD-L1 blockade. However, IL-27 is also known to influence CD4 T cell function, particularly by promoting Th1 and Tr1 differentiation.Methods Here we explored the cell-intrinsic influence of IL-27 on CD4 T cells in the setting of anti-tumor immunity.Results Our data demonstrate that while natural IL-27 signaling as a whole is required for effective tumour-specific CD8 T cell function, endogenous IL-27 signaling in CD4 T cells limits CD8 T cell maintenance and cytotoxic activity at the tumor site. Superphysiological IL-27 stimulation directly induces IFNg production while limiting proliferation of both conventional CD4 T cells and CD4 Treg cells.Conclusions These data highlight the ability of IL-27 to finetune T cell responses and offer mechanistic insights to explain how IL-27 promotes anti-tumour immunity while limiting inflammatory toxicity.
Author: Beatrice Breart
Institution: Genentech
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225205796