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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 Oncoimmunology
2016 ; 5
(10
): e1226719
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CD24 blunts oral squamous cancer development and dampens the functional expansion
of myeloid-derived suppressor cells
#MMPMID27853649
Fugle CW
; Zhang Y
; Hong F
; Sun S
; Westwater C
; Rachidi S
; Yu H
; Garret-Mayer E
; Kirkwood K
; Liu B
; Li Z
Oncoimmunology
2016[]; 5
(10
): e1226719
PMID27853649
show ga
CD24 expression has been implicated in the oncogenesis of multiple types of
cancer and high tumor expression is considered a poor prognosis factor; however,
the role of CD24 in oral cancer progression is unknown. Unlike other cancer
types, we found that higher CD24 levels in human oral cancers are correlated to
lower clinical stage and better overall survival. We then dissected the role of
CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy
and demonstrated that CD24 deficiency increased the oral cavity tumor burden in
response to the carcinogen 4-nitroquioline 1-oxide (4-NQO). Immune profile
analysis showed a significant expansion as well as increased suppressive function
of myeloid-derived suppressor cells (MDSCs) in CD24(-/-) mice, but no apparent
impairment in T cells, B cells, or dendritic cells. Further, studies with an
orthotopically transplanted syngeneic squamous carcinoma model in the tongue of
CD24(-/-) and CD24(+/-) mice confirmed the protective roles of CD24 against
cancer. Moreover, the difference in tumor growth between CD24(-/-) and CD24(+/-)
mice was blunted by immunodepletion of MDSCs. We conclude that CD24 expression
impedes MDSC expansion and function, and thus slows oral cancer oncogenesis. This
study is the first to examine the role of CD24 in a de novo oral cancer model,
and it highlights the need to consider the immune regulatory roles of CD24 in the
development of CD24-targeted therapy for cancer.
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