TY - JOUR
T1 - Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration
AU - Pasikowska, Marta
AU - Walsby, Elisabeth
AU - Apollonio, Benedetta
AU - Cuthill, Kirsty May
AU - Phillips, Elizabeth Helen
AU - Coulter, Eve Marie
AU - Longhi, Maria Serena
AU - Ma, Yun
AU - Yallop, Deborah
AU - Barber, Linda Dorothy
AU - Patten, Piers
AU - Fegan, Christopher
AU - Ramsay, Alan Gregor
AU - Pepper, Chris
AU - Devereux, Stephen
AU - Buggins, Andrea Gail Sherman
PY - 2016/7/28
Y1 - 2016/7/28
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2016-01-683128
DO - 10.1182/blood-2016-01-683128
M3 - Article
SN - 0006-4971
VL - 128
SP - 563
EP - 573
JO - Blood
JF - Blood
IS - 4
ER -