Myeloid leukemia cells with a B7-2(+) subpopulation provoke Th-cell responses and become immuno-suppressive through the modulation of B7 ligands.

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.