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

M Gätjen, F Brand, M Grau, K Gerlach, R Kettritz… - Cancer research, 2016 - AACR
M Gätjen, F Brand, M Grau, K Gerlach, R Kettritz, J Westermann, I Anagnostopoulos, P Lenz…
Cancer research, 2016AACR
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 are 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 is important for malignant progression. In the Eμ-Tcl1 murine model of CLL, we …
Abstract
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 are 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 is important for malignant progression. In the Eμ-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 IL10 and TGFβ. Our results suggest that targeting aberrant neutrophil differentiation and restoring myeloid cell homeostasis could limit the formation of survival niches for CLL cells. Cancer Res; 76(18); 5253–65. ©2016 AACR.
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