title: The CD70/CD27 pathway is critical for stimulation of an effective cytotoxic T cell response against B cell precursor acute lymphoblastic leukemia.
abstract: For effective immunotherapy, maintaining the frequency and cytotoxic potential of effector cells is critical. In this context costimulation via the CD70/CD27 pathway has been proven essential. CD70 has been reported to be expressed to varying degrees on malignant B cells. However, in B cell precursor acute lymphoblastic leukemia, the most common childhood malignancy, the role of CD70 in stimulation of antileukemic T cell responses has so far not been delineated. Herein we demonstrate that in B cell precursor acute lymphoblastic leukemia expression of CD70 is low but can be induced upon blast activation via CD40. Both CD70 and CD80/CD86 up-regulated on CD40-stimulated blasts contribute to primary stimulation of T cell proliferation and cytokine production in an additive manner. These two signals also cooperate in the prevention of T cell anergy. In contrast to blockade of CD70 during the effector phase, inhibition of CD70-mediated costimulation during generation of antileukemic T cells prevents effector cell proliferation and reduces their cytotoxic capacity. Modulation of the CD70/CD27 pathway may thus represent a novel therapeutic approach for augmenting magnitude and quality of the antileukemic response in B cell precursor acute lymphoblastic leukemia.
authors.affiliation: Clinic for Pediatric Oncology, Hematology, and Clinical Immunology, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Glouchkova
authors.forename: Birgit
authors.initials: B
authors.lastname: Ackermann
authors.forename: Andree
authors.initials: A
authors.lastname: Zibert
authors.forename: Roland
authors.initials: R
authors.lastname: Meisel
authors.forename: Meinolf
authors.initials: M
authors.lastname: Siepermann
authors.forename: Gritta E
authors.initials: GE
authors.lastname: Janka-Schaub
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
authors.forename: Anja
authors.initials: A
authors.lastname: Troeger
authors.forename: Dagmar
authors.initials: D
authors.lastname: Dilloo
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D053282:CD27 Ligand / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D053282:CD27 Ligand; C505771:CD70 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7