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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 J+Leukoc+Biol
2016 ; 100
(3
): 463-70
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High-mobility group box protein 1 promotes the survival of myeloid-derived
suppressor cells by inducing autophagy
#MMPMID26864266
Parker KH
; Horn LA
; Ostrand-Rosenberg S
J Leukoc Biol
2016[Sep]; 100
(3
): 463-70
PMID26864266
show ga
Myeloid-derived suppressor cells are immune-suppressive cells that are elevated
in most individuals with cancer, where their accumulation and suppressive
activity are driven by inflammation. As myeloid-derived suppressor cells inhibit
anti-tumor immunity and promote tumor progression, we are determining how their
viability is regulated. Previous studies have established that the
damage-associated molecular pattern molecule high-mobility group box protein 1
drives myeloid-derived suppressor cell accumulation and suppressive potency and
is ubiquitously present in the tumor microenvironment. As high-mobility group box
protein 1 also facilitates tumor cell survival by inducing autophagy, we sought
to determine if high-mobility group box protein 1 regulates myeloid-derived
suppressor cell survival through induction of autophagy. Inhibition of autophagy
increased the quantity of apoptotic myeloid-derived suppressor cells,
demonstrating that autophagy extends the survival and increases the viability of
myeloid-derived suppressor cells. Inhibition of high-mobility group box protein 1
similarly increased the level of apoptotic myeloid-derived suppressor cells and
reduced myeloid-derived suppressor cell autophagy, demonstrating that in addition
to inducing the accumulation of myeloid-derived suppressor cells, high-mobility
group box protein 1 sustains myeloid-derived suppressor cell viability.
Circulating myeloid-derived suppressor cells have a default autophagic phenotype,
and tumor-infiltrating myeloid-derived suppressor cells are more autophagic,
consistent with the concept that inflammatory and hypoxic conditions within the
microenvironment of solid tumors contribute to tumor progression by enhancing
immune-suppressive myeloid-derived suppressor cells. Overall, these results
demonstrate that in addition to previously recognized protumor effects,
high-mobility group box protein 1 contributes to tumor progression by increasing
myeloid-derived suppressor cell viability by driving them into a proautophagic
state.
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