Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25355916
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Immunol
2014 ; 193
(11
): 5723-32
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Tumor-derived ?-fetoprotein impairs the differentiation and T cell stimulatory
activity of human dendritic cells
#MMPMID25355916
Pardee AD
; Shi J
; Butterfield LH
J Immunol
2014[Dec]; 193
(11
): 5723-32
PMID25355916
show ga
Several tumor-derived factors have been implicated in dendritic cell (DC)
dysfunction in cancer patients. ?-fetoprotein (AFP) is an oncofetal Ag that is
highly expressed in abnormalities of prenatal development and several epithelial
cancers, including hepatocellular carcinoma (HCC). In HCC patients exhibiting
high levels of serum AFP, we observed a lower ratio of myeloid/plasmacytoid
circulating DCs compared with patients with low serum AFP levels and healthy
donors. To test the effect of AFP on DC differentiation in vitro, peripheral
blood monocytes from healthy donors were cultured in the presence of cord
blood-derived normal AFP (nAFP) or HCC tumor-derived AFP (tAFP), and DC phenotype
and function were assessed. Although the nAFP and tAFP isoforms only differ at
one carbohydrate group, low (physiological) levels of tAFP, but not nAFP,
significantly inhibited DC differentiation. tAFP-conditioned DCs expressed
diminished levels of DC maturation markers, retained a monocyte-like morphology,
exhibited limited production of inflammatory mediators, and failed to induce
robust T cell proliferative responses. Mechanistic studies revealed that the
suppressive activity of tAFP is dependent on the presence of low molecular mass
(LMM) species that copurify with tAFP and function equivalently to the LMM
fractions of both tumor and nontumor cell lysates. These data reveal the unique
ability of tAFP to serve as a chaperone protein for LMM molecules, both
endogenous and ubiquitous in nature, which function cooperatively to impair DC
differentiation and function. Therefore, novel therapeutic approaches that
antagonize the regulatory properties of tAFP will be critical to enhance immunity
and improve clinical outcomes.