Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration

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Abstract

Several lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype and exhibit enhanced capacity for Tcell activation and superior immune synapse formation when compared to paired peripheralblood samples (PB). LN-derived CLL cells manifest a proliferative, CXCR4dimCD5bright, phenotype compared to those in the PB and higher expression of T-cell activation molecules including CD80, CD86 and HLA-DR. In addition, LN-CLL cells have higher expression of α4β1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergotransendothelial migration (TEM) and enter the proliferation centers of the LNs.Using an in-vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4dimCD5bright with higher CD49d, CD80, CD86 and HLA-DR compared to those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49dhi CLL cells showed enhanced capacity to activate T-cellscompared to CD49dlo sub-populations from the same patient. Thus, although PB-CLL cells have reduced capacity to form immune synapses and activate CD4+ T-cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunological function is not only modulated by microenvironmental interactions but is also a feature of a sub-population of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T-cells.
Original languageEnglish
Pages (from-to)563-573
Number of pages11
JournalBlood
Volume128
Issue number4
Early online date1 Jun 2016
DOIs
Publication statusPublished - 28 Jul 2016

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