High‐mobility group box protein 1 promotes the survival of myeloid‐derived suppressor cells by inducing autophagy

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: tumor‐;    induced immune suppression;    tumor microenvironment;    DAMPs;   

DOI  :  10.1189/jlb.3HI0715-305R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Myeloid‐derivedsuppressorcellsareimmune‐suppressivecellsthatareelevatedinmostindividualswithcancer,wheretheiraccumulationandsuppressiveactivityaredrivenbyinflammation.Asmyeloid‐derivedsuppressorcellsinhibitanti‐tumorimmunityandpromotetumorprogression,wearedetermininghowtheirviabilityisregulated.Previousstudieshaveestablishedthatthedamage‐associatedmolecularpatternmoleculehigh‐mobilitygroupboxprotein1drivesmyeloid‐derivedsuppressorcellaccumulationandsuppressivepotencyandisubiquitouslypresentinthetumormicroenvironment.Ashigh‐mobilitygroupboxprotein1alsofacilitatestumorcellsurvivalbyinducingautophagy,wesoughttodetermineifhigh‐mobilitygroupboxprotein1regulatesmyeloid‐derivedsuppressorcellsurvivalthroughinductionofautophagy.Inhibitionofautophagyincreasedthequantityofapoptoticmyeloid‐derivedsuppressorcells,demonstratingthatautophagyextendsthesurvivalandincreasestheviabilityofmyeloid‐derivedsuppressorcells.Inhibitionofhigh‐mobilitygroupboxprotein1similarlyincreasedthelevelofapoptoticmyeloid‐derivedsuppressorcellsandreducedmyeloid‐derivedsuppressorcellautophagy,demonstratingthatinadditiontoinducingtheaccumulationofmyeloid‐derivedsuppressorcells,high‐mobilitygroupboxprotein1sustainsmyeloid‐derivedsuppressorcellviability.Circulatingmyeloid‐derivedsuppressorcellshaveadefaultautophagicphenotype,andtumor‐infiltratingmyeloid‐derivedsuppressorcellsaremoreautophagic,consistentwiththeconceptthatinflammatoryandhypoxicconditionswithinthemicroenvironmentofsolidtumorscontributetotumorprogressionbyenhancingimmune‐suppressivemyeloid‐derivedsuppressorcells.Overall,theseresultsdemonstratethatinadditiontopreviouslyrecognizedprotumoreffects,high‐mobilitygroupboxprotein1contributestotumorprogressionbyincreasingmyeloid‐derivedsuppressorcellviabilitybydrivingthemintoaproautophagicstate...

【 授权许可】

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