title: Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia.
abstract: Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p<0.0001). The Kaplan-Meier curves for the time to progression and overall survival in groups with high and low surface expression of PD-1 and PD-L1 revealed no prognostic value in CLL patients. After stimulation with IL-4 and CD40L, protein expression of PD-1 was significantly increased in samples that responded and up-regulated CD38. PD-1, which is aberrantly expressed both at mRNA and cell surface levels in CLL cells might represent a novel immunotolerant molecule involved in the pathomechanism of the disease, and could provide a novel target for future therapies.
authors.affiliation: Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Grzywnowicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Zaleska
authors.forename: Daniel
authors.initials: D
authors.lastname: Mertens
authors.forename: Waldemar
authors.initials: W
authors.lastname: Tomczak
authors.forename: Paulina
authors.initials: P
authors.lastname: Wlasiuk
authors.forename: Kamila
authors.initials: K
authors.lastname: Kosior
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Piechnik
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bojarska-Junak
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D019013:CD40 Antigens / Q000494:pharmacology; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D019013:CD40 Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D015847:Interleukin-4