Cancer Research 76 (18): 5253-5265 (2016-09)

Gaetjen M.; Brand F.; Grau M.; Gerlach K.; Kettritz R.; Westermann J.; Anagnostopoulos I.; Lenz P.; Lenz G.; Hoepken U.E.; Rehm A.

Splenic marginal zone granulocytes acquire an accentuated neutrophil B cell-helper phenotype in chronic lymphocytic leukemia.

Recruitment of tumor-associated macrophages and neutrophils (TAM and TAN) to solid tumors contributes to immunosuppression in the tumor microenvironment, however, their contributions to lymphoid neoplasms is less clear. In human chronic lymphocytic leukemia (CLL), tumor B cells lodge in lymph nodes where interactions with the microenvironment occur. Tumor cell homing stimulates proliferation, such that engagement of the B cell receptor are important for malignant progression. In the E{mu}-Tcl1 murine model of CLL, we identified gene expression signatures indicative of a skewed polarization in the phenotype of monocytes and neutrophils. Selective ablation of either of these cell populations in mice delayed leukemia growth. Despite tumor infiltration of these immune cells, a systemic inflammation was not detected. Notably, in progressive CLL splenic neutrophils were observed to differentiate toward a B cell helper phenotype, a process promoted by the induction of leukemia-associated IL-10 and TGF-{beta}. Our results suggest that targeting aberrant neutrophil differentiation and restoring myeloid cell homeostasis could limit the formation of survival niches for CLL cells.

Keywords: Adoptive Transfer, Animal Disease Models, B-Lymphocytes, Cell Differentiation, Cell Separation, Flow Cytometry, Granulocytes, Lymphocytic Chronic B-Cell Leukemia, Neutrophil Activation, Neutrophils, Phenotype, Spleen, Transcriptome, Animals, Mice

Type: Article

PubMed: 27488528
Official URL:
MDC Repository: