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 Blood, 1 May 2005, Vol. 105, No. 9, pp. 3641-3647.
Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-06-2468.

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IMMUNOBIOLOGY

CpG stimulation of precursor B-lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells toward a Th1 response

Gregor S. D. Reid, Kevin She, Luke Terrett, Michael R. Food, Jacqueline D. Trudeau, and Kirk R. Schultz

From the Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia and BC Children's Hospital, Vancouver, BC.

Immunostimulatory DNA containing unmethylated cytosine-phosphate-guanosine (CpG) induces the development of T helper 1 (Th1) immune responses. The response of B cells to CpG stimulation involves increased proliferation, cytokine production, and costimulatory molecule expression. Similar effects have been observed following CpG stimulation of a variety of malignant B cells. Pediatric precursor B acute lymphoblastic leukemia (B-ALL) cells express low levels of costimulatory molecules and are generally poor stimulators of T-cell responses. In this study, we evaluated the impact of CpG stimulation on precursor B-ALL cell lines and pediatric patient-derived samples. The ability to respond to CpG oligodeoxynucleotides was determined by the level of Toll-like receptor 9 (TLR9) expression. In contrast to both nonleukemic B-cell precursors and mature B cells, the response of precursor B-ALL cells was characterized by increased CD40 expression but only small changes in CD86 levels and no induction of CD80 expression. CpG stimulation of ALL blasts produced increased levels of interleukin-6 (IL-6), IL-8, and IL-10 but no detectable IL-12p70 and led to a skewing of allogeneic T cells, with enhanced interferon {gamma} (IFN-{gamma}) production and reduced secretion of IL-5. These results demonstrate the functional relevance of CpG stimulation of precursor B-ALL cells and provide a rational basis for study of these agents for use in treatment of this disease.


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H. Fujii, J. D. Trudeau, D. T. Teachey, J. D. Fish, S. A. Grupp, K. R. Schultz, and G. S. D. Reid
In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides
Blood, March 1, 2007; 109(5): 2008 - 2013.
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