Interleukin-27 potentiates CD8+ T-cell-mediated anti-tumor immunity in chronic lymphocytic leukemia

Giulia Pagano, Iria Fernandez Botana (Main author), Marina Wierz, Philipp M Roessner, Nikolaos Ioannou, Xiangda Zhou, Gheed Al-Hity, Coralie Borne, Ernesto Gargiulo, Susanne Gonder, Bin Qu, Basile Stamatopoulos, Alan G Ramsay, Martina Seiffert, Anne Largeot, Etienne Moussay* (Main author), Jerome Paggetti*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) cells are highly dependent on interactions with the immunosuppressive tumor microenvironment (TME) for survival and proliferation. In the search for novel treatments, pro-inflammatory cytokines have emerged as candidates to reactivate the immune system. Among those, interleukin 27 (IL-27) has recently gained attention, but its effects differ among malignancies. Here, we utilized the Eμ-TCL1 and EBI3 knock-out mouse models as well as clinical samples from patients to investigate the role of IL-27 in CLL. Characterization of murine leukemic spleens revealed that the absence of IL-27 leads to enhanced CLL development and a more immunosuppressive TME in transgenic mice. Gene-profiling of T-cell subsets from EBI3 knock-out highlighted transcriptional changes in the CD8+ T-cell population associated with T-cell activation, proliferation, and cytotoxicity. We also observed an increased anti-tumor activity of CD8+ T cells in the presence of IL-27 ex vivo with murine and clinical samples. Notably, IL-27 treatment led to the reactivation of autologous T cells from CLL patients. Finally, we detected a decrease in IL-27 serum levels during CLL development in both pre-clinical and patient samples. Altogether, we demonstrated that IL-27 has a strong anti-tumorigenic role in CLL and postulate this cytokine as a promising treatment or adjuvant for this malignancy.

Original languageEnglish
Pages (from-to)3011-3024
Number of pages14
JournalHaematologica
Volume108
Issue number11
Early online date22 Jun 2023
DOIs
Publication statusPublished - 1 Nov 2023

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