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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Haematologica
2014 ; 99
(6
): 1078-87
Nephropedia Template TP
gab.com Text
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English Wikipedia
Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor
receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of
immunosuppressive type 2 skewed macrophages
#MMPMID24561793
Giannoni P
; Pietra G
; Travaini G
; Quarto R
; Shyti G
; Benelli R
; Ottaggio L
; Mingari MC
; Zupo S
; Cutrona G
; Pierri I
; Balleari E
; Pattarozzi A
; Calvaruso M
; Tripodo C
; Ferrarini M
; de Totero D
Haematologica
2014[Jun]; 99
(6
): 1078-87
PMID24561793
show ga
Hepatocyte growth factor, produced by stromal and follicular dendritic cells, and
present at high concentrations in the sera of patients with chronic lymphocytic
leukemia, prolongs the survival of leukemic B cells by interacting with their
receptor, c-MET. It is, however, unknown whether hepatocyte growth factor
influences microenvironmental cells, such as nurse-like cells, which deliver
survival signals to the leukemic clone. We evaluated the expression of c-MET on
nurse-like cells and monocytes from patients with chronic lymphocytic leukemia
and searched for phenotypic/functional features supposed to be influenced by the
hepatocyte growth factor/c-MET interaction. c-MET is expressed at high levels on
nurse-like cells and at significantly higher levels than normal on monocytes from
patients. Moreover, the hepatocyte growth factor/c-MET interaction activates
STAT3(TYR705) phosphorylation in nurse-like cells. Indoleamine 2,3-dioxygenase,
an enzyme modulating T-cell proliferation and induced on normal monocytes after
hepatocyte growth factor treatment, was detected together with interleukin-10 on
nurse-like cells, and on freshly-prepared patients' monocytes.
Immunohistochemical/immunostaining analyses demonstrated the presence of c-MET(+)
and indoleamine 2,3-dioxygenase(+) cells in lymph node biopsies, co-expressed
with CD68 and vimentin. Furthermore nurse-like cells and chronic lymphocytic
monocytes significantly inhibited T-cell proliferation, prevented by
anti-transforming growth factor beta and interleukin-10 antibodies and
indoleamine 2,3-dioxygenase inhibitors, and supported CD4(+)CD25(high+)/FOXP3(+)
T regulatory cell expansion. We suggest that nurse-like cells display features of
immunosuppressive type 2 macrophages: higher hepatocyte growth factor levels,
produced by leukemic or other microenvironmental surrounding cells, may cooperate
to induce M2 polarization. Hepatocyte growth factor may thus have a dual
pathophysiological role: directly through enhancement of survival of the leukemic
clone and indirectly by favoring T-cell immunosuppression.
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