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

[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...

[学科分类] 生理学

[关键词] tumor‐induced immune suppression;tumor microenvironment;DAMPs