title: Complementary IL-23 and IL-27 anti-tumor activities cause strong inhibition of human follicular and diffuse large B-cell lymphoma growth in vivo.
abstract: Interleukin (IL)-23 and IL-27 are pro-inflammatory cytokines that share functional and structural similarities and may exert anti-tumor activities against solid and hematological malignancies. Here, we asked whether IL-23 and IL-27, alone or in combination, may act directly against human follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) cells. In this study, we demonstrated for the first time that human primary FL and DLBCL cells expressed complete and functional IL-23 and IL-27 receptors (R) and that IL-23 and IL-27 exerted anti-tumor activities in vitro and in vivo through different and complementary mechanisms. In vivo studies using severe combined immunodeficiency /non-obese diabetic mice-injected subcutaneously with human SU-DHL-4 cell line revealed that IL-23 inhibited directly tumor-cell proliferation, whereas IL-27 impaired the angiogenic program of lymphoma cells resulting in strong reduction of cell growth. In addition, combined treatment of IL-23 and IL-27 amplified the anti-tumor effects in vivo as compared with administration of each cytokine alone. These anti-tumor mechanisms were confirmed by in vitro experiments performed with primary lymphoma cells and cell lines. Our results strongly encourage the development of future clinical trials to evaluate the toxicity and efficacy of the IL-23 and IL-27 in lymphoma patients.
authors.affiliation: AIRC Laboratory of Immunology and Tumors, Department of Experimental and Laboratory Medicine, G Gaslini Institute, Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cocco
authors.forename: E
authors.initials: E
authors.lastname: Di Carlo
authors.forename: S
authors.initials: S
authors.lastname: Zupo
authors.forename: S
authors.initials: S
authors.lastname: Canale
authors.forename: A
authors.initials: A
authors.lastname: Zorzoli
authors.forename: D
authors.initials: D
authors.lastname: Ribatti
authors.forename: F
authors.initials: F
authors.lastname: Morandi
authors.forename: E
authors.initials: E
authors.lastname: Ognio
authors.forename: I
authors.initials: I
authors.lastname: Airoldi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002645:Chickens; D049033:Chorioallantoic Membrane; D004273:DNA, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D020381:Interleukin-17 / Q000627:therapeutic use*; D053759:Interleukin-23 / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D042501:Angiogenic Proteins; D004273:DNA, Neoplasm; D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger