REVIEWOpenAccessPyroptosisattheforefrontofanticancerimmunityReidLoveless1,RyanBloomquist2andYongTeng3*AbstractTumorresistancetoapoptosisandtheimmunosuppressivetumormicroenvironmentaretwomajorcontributorstopoortherapeuticresponsesduringcancerintervention.Pyroptosis,alyticandinflammatoryprogrammedcelldeathpathwaydistinctfromapoptosis,hassubsequentlysparkednotableinterestamongcancerresearchersforitspotentialtobeclinicallyharnessedandtoaddresstheseproblems.Recentevidenceindicatesthatpyroptosisinductionintumorcellsleadstoarobustinflammatoryresponseandmarkedtumorregression.Underlyingitsantitumoreffect,pyroptosisismediatedbypore-forminggasderminproteinsthatfacilitateimmunecellactivationandinfiltrationthroughtheirreleaseofpro-inflammatorycytokinesandimmunogenicmaterialfollowingcellrupture.Consideringitsinflammatorynature,however,aberrantpyroptosismayalsobeimplicatedintheformationofatumorsupportivemicroenvironment,asevidencedbytheupregulationofgasderminproteinsincertaincancers.Inthisreview,themolecularpathwaysleadingtopyroptosisareintroduced,followedbyanoverviewoftheseeminglyentangledlinksbetweenpyroptosisandcancer.Wedescribewhatisknownregardingtheimpactofpyroptosisonanticancerimmunityandgiveinsightintothepotentialofharnessingpyroptosisasatoolandapplyingittonovelorexistinganticancerstrategies.Keywords:Pyroptosis,Antitumorimmunity,Gasdermin,cancer,TheimmunelandscapeBackgroundWhilelongevadingdiscovery,theexistenceandphysio-logicalsignificanceofprogrammedcelldeath(PCD)pathwaysdistinctfromapoptosishavegarneredincreas-inginterestinrecentyears,inpart,duetothehighprevalenceofapoptosisresistanceintumors[1].Ofthesedifferentforms,pyroptosis,anecroticandlyticPCD,hasdistinguisheditselffromothersbyitsabilitytoinduceapowerfulinflammatoryresponse[2].Similartonecroptosis,aprogrammedformofnecrosis,pyroptosisisbelievedtoexistprincipallyasadefenseagainstpatho-gensbytriggeringanantimicrobialresponsethroughthereleaseofimmunogeniccellularcontent,includingdamage-associatedmolecularpatterns(DAMP...
