CCL3 chemokine expression by chronic lymphocytic leukemia cells orchestrates the composition of the microenvironment in lymph node infiltrates

Abstract

Previous experiments demonstrated that survival and proliferation of chronic lymphocytic leukemia (CLL) cells depends upon complex cross-talk between CLL cells and accessory cells in the tissue microenvironment. To further dissect these interactions in situ, we analyzed lymph nodes from 43 different patients infiltrated by CLL cells for expression of the chemokine CCL3, Ki-67, macrophages, and T cell subsets by immunohistochemistry. CCL3 expression was detected in 24 of 43 cases (56%), particularly in prolymphocytes and paraimmunoblasts within the proliferation centers. Significantly higher numbers of CD3+ T cells and CD57+ cells were noticed in CCL3 positive cases. Furthermore, denser infiltration of CLL lymph node tissues by CD57+ cells correlated with higher proliferation rates of the CLL cells. In conclusion, we demonstrate an association of CCL3 expression by CLL cells with increased numbers of CD3+ T cells and CD57+ cells in the lymph node microenvironment, which may promote CLL cell survival and proliferation.

Keywords:

• CD57
• CCL3
• CLL
• lymph node microenvironment
• T cells

Acknowledgements

We thank Theodora Nedeva and Sabine Roth for excellent technical assistance. This study was supported by a CLL Global Research Foundation grant (Title: Cellular characterization of the microenvironment in chronic lymphocytic leukemia (CLL): Who are the key players and how do they look?).

Potential conflict of interest:

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Supplementary material available online

Figures 1-2 and Table showing further data.