TY - JOUR
T1 - Interleukin-27 potentiates CD8+ T-cell-mediated anti-tumor immunity in chronic lymphocytic leukemia
AU - Pagano, Giulia
AU - Botana, Iria Fernandez
AU - Wierz, Marina
AU - Roessner, Philipp M
AU - Ioannou, Nikolaos
AU - Zhou, Xiangda
AU - Al-Hity, Gheed
AU - Borne, Coralie
AU - Gargiulo, Ernesto
AU - Gonder, Susanne
AU - Qu, Bin
AU - Stamatopoulos, Basile
AU - Ramsay, Alan G
AU - Seiffert, Martina
AU - Largeot, Anne
AU - Moussay, Etienne
AU - Paggetti, Jerome
N1 - Disclosures: This work was supported by grants from FNRS-Télévie to GP (7.4501.18, 7.6518.20), IFB (7.4529.19, 7.6603.21), MW (7.4508.16, 7.6504.18), SG (7.4502.19, 7.6604.21), CB (7.4577.22), and AL (7.4502.17, 7.4503.19), and from the Luxembourg National Research Fund (FNR) and Fondation Cancer to EG, EM and JP (PRIDE15/10675146/CANBIO, C20/BM/14582635, and C20/BM/14592342
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175724642&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37345470
U2 - 10.3324/haematol.2022.282474
DO - 10.3324/haematol.2022.282474
M3 - Article
C2 - 37345470
SN - 0390-6078
VL - 108
SP - 3011
EP - 3024
JO - Haematologica
JF - Haematologica
IS - 11
ER -