title: Myeloid leukemia cells with a B7-2(+) subpopulation provoke Th-cell responses and become immuno-suppressive through the modulation of B7 ligands.
abstract: Expression of the B7 family molecules in acute myeloid leukemia (AML) has been demonstrated by independent clinical studies. Intriguingly, the expression of the most potent costimulatory molecules B7-2 (CD86) and B7-H2 (ICOS Ligand) on AML cells has been associated with poor prognosis and disease severity. Here, this phenomenon was modeled in vitro with the myeloid leukemia cell line HL-60, which is capable of differentiating through the FAB M2/M3 and M4/M5 immunophenotypes. These derivatives of HL-60 harbored a B7-2(+) subpopulation and recapitulated the distribution of B7 ligands previously reported in primary AML cases. B7-2(+) AML cells significantly contributed to T-cell responses. This costimulatory activity enabled helper (Th)-cell activation, proliferation, and production of Th1-associated cytokines. Conversely, even a short-term incubation with stimulated T cells resulted in upregulation of inhibitory B7-H1 (PD-L1) and B7-DC (PD-L2), and downregulation of stimulatory B7-H2 molecules on leukemia cells. Purified from iHL-60-T-cell co-cultures, these myeloid leukemia cells severely suppressed Th-cell responses specifically through the PD-1 pathway. In conclusion, Th-cell responses can be directly supported by B7-2(+) leukemia subpopulations. However, this interaction can facilitate the acquisition of a suppressive character that may contribute to immune evasion in myeloid leukemia.
authors.affiliation: Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Dolen
authors.forename: Gunes
authors.initials: G
authors.lastname: Esendagli
mesh_terms: D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D007108:Immune Tolerance; D007951:Leukemia, Myeloid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D008024:Ligands; D061026:Programmed Cell Death 1 Receptor; D011493:Protein Kinase C