• Aucun résultat trouvé

Souris :

>es souris MMds-Eeu de fond généƟƋue >ͬc obtenues du laboratoire du Wrof͘ &ede-rica avallo et les souris caspase-1 obtenues du laboratoire du Wr͘ Zichard ͘ &lavell ont été croi-sées aĮn d͛obtenir des souris caspase-1/caspase-11-ͬ- MMTV-Neuн et caspase-1/caspase-11нͬн

MMTV-Neuн͘ >͛appariƟon de tumeurs est surveillée dans les glandes mammaires trois fois par

semaine dés le sevrage des souris femelles͘ Une masse dont le plus grand des diamètres edžcède 3mm est considérée comme une tumeur͘

InũecƟon d͛AnaŬinra :

Une soluƟon d͛anaŬinra diluée dans du WS est réalisée à 4mgͬm>͘ Un ũour avant l͛inũec-Ɵon des cellules 4d1͕ la souris sont traitées en /W avec 2Ϭmgͬg d͛naŬinra (volume с 5 Ύ poids de la souris en mgͿ͘ >es traitements sont eīectués ensuite tous les 2 ũours en /W͘ omme pour les autres edžpériences de croissance tumorale͕ 1Ϭ ϬϬϬ cellules 4d1 (1ϬϬ ʅ>Ϳ sont inũectées dans la glande mammaire et le suivi des tumeurs est eīectué par mesure au pied à coulisse͘

Culture cellulaire :

>es cellules K771 sont culƟvées dans du milieu MM supplémenté avec 1Ϭй (vͬvͿ de sérum de veau fƈtal inacƟvé͕ 1й (vͬvͿ glutamadž͕ 1й (vͬvͿ pénicillineͬstreptomLJcine dans un incubateur à 5й K2 et 37Σ͘ vant inũecƟon͕ les cellules sont sLJstémaƟƋuement testées pour la présence de mLJcoplasmes (MLJcolert MLJcoplasma detecƟon Ŭit͕ >onnjaͿ͘ >es lignées sont aussi saines de tout agents infecƟeudž murins (daƋman WZ tesƟng of mouse essenƟal panel͕ harles ZiverͿ͘

InũecƟons des cellules EKϳϳ1 :

>es cellules K771 sont récoltées et reprises dans du WS à 2͘1Ϭϲ cellulesͬm>͘ 1ϬϬ ʅ> de ceƩe soluƟon sont inũectées directement dans la glande mammaire de souris 57lͬϲ td ou

caspase-1 <K͘ >a croissance des cellules est suivie par mesure au pied à coulisse͘ >es souris sont

14Ϭ

-REFERENCES

A

bdullah͕ ͕͘ Schlee͕ M͕͘ Zoth͕ S͕͘ Mraheil͕ M͕͘͘ archet͕ t͕͘ ƂƩcher͕ J͕͘ ,ain͕ d͕͘ 'eiger͕ S͕͘ ,aLJaŬaǁa͕ z͕͘ &ritnj͕ J͘,͕͘ et al͘ (2Ϭ12Ϳ͘ Z/'-/ detects infecƟon ǁith live >isteria bLJ sensing se-creted bacterial nucleic acids͘ MK J͘ 31͕ 4153ʹ41ϲ4͘

blasser͕ ͕͘ 'oldecŬ͕ M͕͘ avlar͕ d͕͘ eimling͕ d͕͘ tiƩe͕ '͕͘ ZƂhl͕ /͕͘ ,opfner͕ <͘-W͕͘ >udǁig͕ J͕͘ and ,ornung͕ s͘ (2Ϭ13Ϳ͘ c'S produces a 2͛-5͛-linŬed cLJclic dinucleoƟde second messenger that acƟvates Sd/E'͘ Eature 498͕ 38Ϭʹ384͘

dler͕ ͘W͕͘ >emŬen͕ ͕͘͘ <atchen͕ E͘S͕͘ and <urt͕ Z͘͘ (2ϬϬ3Ϳ͘  dual role for tumor-derived che-moŬine ZEdS (>5Ϳ͘ /mmunol͘ >eƩ͘ 9Ϭ͕ 187ʹ194͘

gosƟni͕ >͕͘ MarƟnon͕ &͕͘ urns͕ <͕͘ McermoƩ͕ M͘&͕͘ ,aǁŬins͕ W͘E͕͘ and dschopp͕ J͘ (2ϬϬ4Ϳ͘ E>W3 forms an />-1beta-processing inŇammasome ǁith increased acƟvitLJ in MucŬle-tells autoinŇammatorLJ disorder͘ /mmunitLJ 2Ϭ͕ 319ʹ325͘

llen͕ /͕͘͘ Scull͕ M͕͘͘ Moore͕ ͕͘͘ ,oll͕ ͘<͕͘ Mclvania-de<ippe͕ ͕͘ dadžman͕ ͘J͕͘ 'uthrie͕ ͘,͕͘ WicŬles͕ Z͘J͕͘ and ding͕ J͘W͘-z͘ (2ϬϬ9Ϳ͘ dhe E>ZW3 inŇammasome mediates in vivo innate immu-nitLJ to inŇuennja  virus through recogniƟon of viral ZE͘ /mmuimmu-nitLJ 3Ϭ͕ 55ϲʹ5ϲ5͘

llen͕ /͕͘͘ de<ippe͕ ͘M͕͘ toodford͕ Z͘-M͘d͕͘ Uronis͕ J͘M͕͘ ,oll͕ ͘<͕͘ Zogers͕ ͕͘͘ ,erfarth͕ ,͘,͕͘ Jobin͕ ͕͘ and ding͕ J͘W͘-z͘ (2Ϭ1ϬͿ͘ dhe E>ZW3 inŇammasome funcƟons as a negaƟve regulator of tumorigenesis during coliƟs-associated cancer͘ J͘ džp͘ Med͘ 2Ϭ7͕ 1Ϭ45ʹ1Ϭ5ϲ͘

lmand͕ ͕͘ larŬ͕ J͘/͕͘ EiŬiƟna͕ ͕͘ van eLJnen͕ J͕͘ nglish͕ E͘Z͕͘ <night͕ S͕͘͘ arbone͕ ͘W͕͘ and 'abrilovich͕ ͘/͘ (2ϬϬ1Ϳ͘ /ncreased producƟon of immature mLJeloid cells in cancer paƟents͗ a mechanism of immunosuppression in cancer͘ J͘ /mmunol͘ 1ϲϲ͕ ϲ78ʹϲ89͘

mo͕ >͕͘ damaLJo-Krbegonjo͕ ͕͘ Maruri͕ E͕͘ uƋué͕ ͕͘ Solaun͕ M͕͘ ZiŹſn͕ M͕͘ rrieta͕ ͕͘ and >ar-rucea͕ S͘ (2Ϭ15Ϳ͘ WodocalLJdžin-liŬe protein 1 funcƟons as an immunomodulatorLJ molecule in breast cancer cells͘ ancer >eƩ͘ 3ϲ8͕ 2ϲʹ35͘

mulic͕ ͕͘ anjalet͕ ͕͘ ,aLJes͕ '͘>͕͘ Metnjler͕ <͕͘͘ and LJchlinsŬLJ͕ ͘ (2Ϭ12Ϳ͘ Eeutrophil funcƟon͗ from mechanisms to disease͘ nnu͘ Zev͘ /mmunol͘ 3Ϭ͕ 459ʹ489͘

negſn͕ /͕͘ uturi͕ M͕͘͘ drinchieri͕ '͕͘ and Werussia͕ ͘ (1988Ϳ͘ /nteracƟon of &c receptor (1ϲͿ ligands induces transcripƟon of interleuŬin 2 receptor (25Ϳ and lLJmphoŬine genes and edž-pression of their products in human natural Ŭiller cells͘ J͘ džp͘ Med͘ 1ϲ7͕ 452ʹ472͘

ntonopoulos͕ ͕͘ Zusso͕ ,͘M͕͘ l Sanadi͕ ͕͘ MarƟn͕ ͘E͕͘ >i͕ y͕͘ <aiser͕ t͘J͕͘ MocarsŬi͕ ͘S͕͘ and ubLJaŬ͕ '͘Z͘ (2Ϭ15Ϳ͘ aspase-8 as an īector and Zegulator of E>ZW3 /nŇammasome Signa-ling͘ J͘ iol͘ hem͘ 29Ϭ͕ 2Ϭ1ϲ7ʹ2Ϭ184͘

pte͕ Z͘E͕͘ otan͕ S͕͘ lŬabets͕ M͕͘ thite͕ M͘Z͕͘ Zeich͕ ͕͘ armi͕ z͕͘ Song͕ y͕͘ vonjŬin͕ d͕͘ <relin͕ z͕͘ and soronov͕ ͘ (2ϬϬϲͿ͘ dhe involvement of />-1 in tumorigenesis͕ tumor invasiveness͕ me-tastasis and tumor-host interacƟons͘ ancer Meme-tastasis Zev͘ 25͕ 387ʹ4Ϭ8͘

slaŬson͕ ͘J͕͘ and Miller͕ &͘Z͘ (1992Ϳ͘ SelecƟve events in the metastaƟc process deĮned bLJ ana-lLJsis of the seƋuenƟal disseminaƟon of subpopulaƟons of a mouse mammarLJ tumor͘ ancer Zes͘ 52͕ 1399ʹ14Ϭ5͘

LJala͕ J͘M͕͘ zamin͕ d͘d͕͘ gger͕ >͕͘͘ hin͕ J͕͘ <ostura͕ M͘J͕͘ and Miller͕ ͘<͘ (1994Ϳ͘ />-1 beta-conver-Ɵng ennjLJme is present in monocLJƟc cells as an inacƟve 45-Ŭa precursor͘ J͘ /mmunol͘ 153͕ 2592ʹ2599͘

B

aroũa-Manjo͕ ͕͘ Marơn-SĄnchenj͕ &͕͘ 'omenj͕ ͘/͕͘ Marơnenj͕ ͘M͕͘ mores-/niesta͕ J͕͘ ompan͕ s͕͘ arberà-remades͕ M͕͘ zagƺe͕ J͕͘ Zuinj-KrƟnj͕ ͕͘ ntſn͕ J͕͘ et al͘ (2Ϭ14Ϳ͘ dhe E>ZW3 inŇamma-some is released as a parƟculate danger signal that ampliĮes the inŇammatorLJ response͘ Eat͘ /mmunol͘ 15͕ 738ʹ748͘

aselga͕ J͕͘ lbanell͕ J͕͘ Molina͕ M͕͘͘ and rribas͕ J͘ (2ϬϬ1Ϳ͘ Mechanism of acƟon of trastunjumab and scienƟĮc update͘ Semin͘ Kncol͘ 28͕ 4ʹ11͘

auer͕ S͕͘ 'roh͕ s͕͘ tu͕ J͕͘ Steinle͕ ͕͘ Whillips͕ J͘,͕͘ >anier͕ >͘>͕͘ and Spies͕ d͘ (1999Ϳ͘ cƟvaƟon of E< cells and d cells bLJ E<'2͕ a receptor for stress-inducible M/͘ Science 285͕ 727ʹ729͘ auernfeind͕ &͘'͕͘ ,orvath͕ '͕͘ Stutnj͕ ͕͘ lnemri͕ ͘S͕͘ Maconald͕ <͕͘ Speert͕ ͕͘

&er-nandes-lnemri͕ d͕͘ tu͕ J͕͘ MonŬs͕ ͘'͕͘ &itnjgerald͕ <͕͘͘ et al͘ (2ϬϬ9Ϳ͘ uƫng edge͗ E&-Ŭap-pa acƟvaƟng paƩern recogniƟon and cLJtoŬine receptors license E>ZW3 inŇammasome acƟ-vaƟon bLJ regulaƟng E>ZW3 edžpression͘ J͘ /mmunol͘ 183͕ 787ʹ791͘

aum͕ Z͕͘ Sharma͕ S͕͘ arpenter͕ S͕͘ >i͕ Y͘-͕͘ usto͕ W͕͘ &itnjgerald͕ <͕͘͘ MarshaŬ-Zothstein͕ ͕͘ and 'ravallese͕ ͘M͘ (2Ϭ15Ϳ͘ uƫng edge͗ /M2 and endosomal d>Zs diīerenƟallLJ regulate arthriƟs and autoanƟbodLJ producƟon in Ease //-deĮcient mice͘ J͘ /mmunol͘ 194͕ 873ʹ877͘ ecŬhove͕ W͕͘ &euerer͕ M͕͘ olenc͕ M͕͘ Schuetnj͕ &͕͘ hoi͕ ͕͘ Sommerfeldt͕ E͕͘ Schǁendemann͕ J͕͘

hlert͕ <͕͘ ltevogt͕ W͕͘ astert͕ '͕͘ et al͘ (2ϬϬ4Ϳ͘ SpeciĮcallLJ acƟvated memorLJ d cell subsets from cancer paƟents recogninje and reũect dženotransplanted autologous tumors͘ J͘ lin͘ /nvest͘ 114͕ ϲ7ʹ7ϲ͘

elot͕ ͕͘ 'rosclaude͕ W͕͘ ossard͕ E͕͘ Jougla͕ ͕͘ enhamou͕ ͕͘ elafosse͕ W͕͘ 'uinjard͕ ͘-s͕͘ Mo-linié͕ &͕͘ annjon͕ ͕͘ ara͕ S͕͘ et al͘ (2ϬϬ8Ϳ͘ ancer incidence and mortalitLJ in &rance over the period 198Ϭʹ2ϬϬ5͘ Zev͘ pidemiol͘ Sante WubliƋue 5ϲ͕ 159ʹ175͘

lacŬ͕ Z͕͘͘ <ronheim͕ S͘Z͕͘ Merriam͕ J͕͘͘ March͕ ͘J͕͘ and ,opp͕ d͘W͘ (1989Ϳ͘  pre-aspartate-spe-ciĮc protease from human leuŬocLJtes that cleaves pro-interleuŬin-1 beta͘ J͘ iol͘ hem͘ 2ϲ4͕ 5323ʹ532ϲ͘

odnar-tachtel͕ M͘ (2Ϭ15Ϳ͘ tude du rôle de E>ZW3 dans la tumorigenèse pulmonaire͘ dhèse de doctorat en biologie͕ nΣ d͛ordre 184-2Ϭ15͕ Université laude ernard >LJon 1͘

>KKM͕ ,͘J͕͘ and Z/,ZSKE͕ t͘t͘ (1957Ϳ͘ ,istological grading and prognosis in breast cancer͖ a studLJ of 14Ϭ9 cases of ǁhich 359 have been folloǁed for 15 LJears͘ r͘ J͘ ancer 11͕ 359ʹ377͘ oatright͕ <͘M͕͘ and Salvesen͕ '͘S͘ (2ϬϬ3Ϳ͘ Mechanisms of caspase acƟvaƟon͘ urr͘ Kpin͘ ell

iol͘ 15͕ 725ʹ731͘

oggio͕ <͕͘ Eicoleƫ͕ '͕͘ i arlo͕ ͕͘ avallo͕ &͕͘ >andunjnji͕ >͕͘ Melani͕ ͕͘ 'iovarelli͕ M͕͘ Zossi͕ /͕͘ Eanni͕ W͕͘ e 'iovanni͕ ͕͘ et al͘ (1998Ϳ͘ /nterleuŬin 12-mediated prevenƟon of spontaneous mammarLJ adenocarcinomas in tǁo lines of ,er-2ͬneu transgenic mice͘ J͘ džp͘ Med͘ 188͕ 589ʹ 59ϲ͘

oudreau͕ ,͕͘͘ roustas͕ ͘'͕͘ 'oŬhale͕ W͕͘͘ <umar͕ ͕͘ Meǁani͕ Z͘Z͕͘ Zone͕ J͕͘͘ ,addad͕ ͘Z͕͘ and <asid͕ U͘ (2ϬϬ7Ϳ͘ džpression of Z3͕ a novel cell cLJcle regulated molecule͕ is associated ǁith increased phospho-Z< and cell proliferaƟon͘ /nt͘ J͘ Mol͘ Med͘ 19͕ 29ʹ39͘

ourgeois͕ ͕͘ san͕ >͘W͕͘ Samson͕ M͕͘ iem͕ S͕͘ arra͕ ͕͘ Zoga͕ S͕͘ 'ombert͕ J͘-M͕͘ Schneider͕ ͕͘ LJ͕ M͕͘ 'ourdLJ͕ W͕͘ et al͘ (2ϬϬ9Ϳ͘ dhe pro-dh2 cLJtoŬine />-33 directlLJ interacts ǁith invariant E<d and E< cells to induce /&E-gamma producƟon͘ ur͘ J͘ /mmunol͘ 39͕ 1Ϭ4ϲʹ1Ϭ55͘

an 142 an

-rennan͕ M͕͘͘ and ooŬson͕ ͘d͘ (2ϬϬϬͿ͘ Salmonella induces macrophage death bLJ caspase-1-de-pendent necrosis͘ Mol͘ Microbiol͘ 38͕ 31ʹ4Ϭ͘

rough͕ ͕͘ and Zothǁell͕ E͘J͘ (2ϬϬ7Ϳ͘ aspase-1-dependent processing of pro-interleuŬin-1beta is cLJtosolic and precedes cell death͘ J͘ ell Sci͘ 12Ϭ͕ 772ʹ781͘

roǁn͕ '͕͘͘ daLJlor͕ W͘Z͕͘ Zeid͕ ͘M͕͘ tillment͕ J͕͘͘ tilliams͕ ͘>͕͘ MarƟnenj-Womares͕ >͕͘ tong͕ S͘z͕͘͘ and 'ordon͕ S͘ (2ϬϬ2Ϳ͘ ecƟn-1 is a maũor beta-glucan receptor on macrophages͘ J͘ džp͘ Med͘ 19ϲ͕ 4Ϭ7ʹ412͘

ronj͕ W͕͘ von MoltŬe͕ J͕͘ Jones͕ J͘t͕͘ sance͕ Z͕͘͘ and MonacŬ͕ ͘M͘ (2Ϭ1ϬͿ͘ iīerenƟal reƋuire-ment for aspase-1 autoproteolLJsis in pathogen-induced cell death and cLJtoŬine processing͘ ell ,ost Microbe 8͕ 471ʹ483͘

ronj͕ W͕͘ ZubLJ͕ d͕͘ elhocine͕ <͕͘ ouleLJ͕ ͘M͕͘ <aLJagaŬi͕ E͕͘ idžit͕ s͘M͕͘ and MonacŬ͕ ͘M͘ (2Ϭ12Ϳ͘ aspase-11 increases suscepƟbilitLJ to Salmonella infecƟon in the absence of caspase-1͘ Ea-ture 49Ϭ͕ 288ʹ291͘

ruchard͕ M͕͘ Mignot͕ '͕͘ erangère͕ s͕͘ halmin͕ &͕͘ hevriaudž͕ ͕͘ ségran͕ &͕͘ oireau͕ t͕͘ Simon͕ ͕͘ ZLJīel͕ ͕͘ onnat͕ J͘>͕͘ et al͘ (2Ϭ13Ϳ͘ hemotherapLJ-triggered cathepsin  release in mLJe-loid-derived suppressor cells acƟvates the Elrp3 inŇammasome and promotes tumor groǁth͘ Eat͘ Med͘ 19͕ 57ʹϲ4͘

van der ruggen͕ W͕͘ draversari͕ ͕͘ homenj͕ W͕͘ >urƋuin͕ ͕͘ e Wlaen͕ ͕͘ san den LJnde͕ ͕͘ <nuth͕ ͕͘ and oon͕ d͘ (1991Ϳ͘  gene encoding an anƟgen recogninjed bLJ cLJtolLJƟc d lLJmphocLJtes on a human melanoma͘ Science 254͕ 1ϲ43ʹ1ϲ47͘

ulau͕ ͘-M͕͘ Eold͕ M͘&͕͘ >i͕ S͕͘ Eold-WetrLJ͕ ͕͘͘ &inŬ͕ M͕͘ Mansell͕ ͕͘ Schǁerd͕ d͕͘ ,ong͕ J͕͘ Zu-bartelli͕ ͕͘ inarello͕ ͕͘͘ et al͘ (2Ϭ14Ϳ͘ Zole of caspase-1 in nuclear translocaƟon of />-37͕ release of the cLJtoŬine͕ and />-37 inhibiƟon of innate immune responses͘ Wroc͘ Eatl͘ cad͘ Sci͘ U͘ S͘ ͘ 111͕ 2ϲ5Ϭʹ2ϲ55͘

unt͕ S͘<͕͘ Sinha͕ W͕͘ lements͕ s͘<͕͘ >eips͕ J͕͘ and Kstrand-Zosenberg͕ S͘ (2ϬϬϲͿ͘ /nŇammaƟon induces mLJeloid-derived suppressor cells that facilitate tumor progression͘ J͘ /mmunol͘ 17ϲ͕ 284ʹ29Ϭ͘

unt͕ S͘<͕͘ zang͕ >͕͘ Sinha͕ W͕͘ lements͕ s͘<͕͘ >eips͕ J͕͘ and Kstrand-Zosenberg͕ S͘ (2ϬϬ7Ϳ͘ Zeduced inŇammaƟon in the tumor microenvironment delaLJs the accumulaƟon of mLJeloid-derived suppressor cells and limits tumor progression͘ ancer Zes͘ ϲ7͕ 1ϬϬ19ʹ1ϬϬ2ϲ͘

ƺrcŬstƺmmer͕ d͕͘ aumann͕ ͕͘ lƺml͕ S͕͘ idžit͕ ͕͘ ƺrnberger͕ '͕͘ Jahn͕ ,͕͘ WlanLJavsŬLJ͕ M͕͘ ilban͕ M͕͘ olinge͕ J͕͘ enneƩ͕ <͘>͕͘ et al͘ (2ϬϬ9Ϳ͘ n orthogonal proteomic-genomic screen idenƟĮes /M2 as a cLJtoplasmic E sensor for the inŇammasome͘ Eat͘ /mmunol͘ 1Ϭ͕ 2ϲϲʹ272͘

C

ai͕ y͕͘ hen͕ J͕͘ yu͕ ,͕͘ >iu͕ S͕͘ Jiang͕ Y͘-y͕͘ ,alfmann͕ Z͕͘ and hen͕ ͘J͘ (2Ϭ14Ϳ͘ Wrion-liŬe polLJme-rinjaƟon underlies signal transducƟon in anƟviral immune defense and inŇammasome acƟva-Ɵon͘ ell 15ϲ͕ 12Ϭ7ʹ1222͘

armi͕ z͕͘ otan͕ S͕͘ Zider͕ W͕͘ <aplanov͕ /͕͘ thite͕ M͘Z͕͘ aron͕ Z͕͘ butbul͕ S͕͘ ,usnjar͕ M͕͘ inarel-lo͕ ͕͘͘ pte͕ Z͘E͕͘ et al͘ (2Ϭ13Ϳ͘ dhe role of />-1ɴ in the earlLJ tumor cell-induced angiogenic response͘ J͘ /mmunol͘ 19Ϭ͕ 35ϬϬʹ35Ϭ9͘

arriere͕ s͕͘ Zoussel͕ >͕͘ Krtega͕ E͕͘ >acorre͕ ͘-͕͘ merich͕ >͕͘ guilar͕ >͕͘ ouche͕ '͕͘ and 'i-rard͕ J͘-W͘ (2ϬϬ7Ϳ͘ />-33͕ the />-1-liŬe cLJtoŬine ligand for Sd2 receptor͕ is a chromaƟn-associated nuclear factor in vivo͘ Wroc͘ Eatl͘ cad͘ Sci͘ U͘ S͘ ͘ 1Ϭ4͕ 282ʹ287͘

aruso͕ Z͕͘ tarner͕ E͕͘ /nohara͕ E͕͘ and EƷŹenj͕ '͘ (2Ϭ14Ϳ͘ EK1 and EK2͗ signaling͕ host de-fense͕ and inŇammatorLJ disease͘ /mmunitLJ 41͕ 898ʹ9Ϭ8͘

ase͕ ͘>͕͘ <ohler͕ >͘J͕͘ >ima͕ J͕͘͘ Stroǁig͕ d͕͘ de oete͕ M͘Z͕͘ &lavell͕ Z͕͘͘ amboni͕ ͘S͕͘ and ZoLJ͕ ͘Z͘ (2Ϭ13Ϳ͘ aspase-11 sƟmulates rapid Ňagellin-independent pLJroptosis in response to >e-gionella pneumophila͘ Wroc͘ Eatl͘ cad͘ Sci͘ U͘ S͘ ͘ 11Ϭ͕ 1851ʹ185ϲ͘

Sz͕ ͕͘͘ >SdZ͕ t͘Z͕͘ and ZKSS͕ '͘>͘ (1951Ϳ͘ Sustained enhanced groǁth of carcinoma K771 in 57 blacŬ mice͘ Wroc͘ Soc͘ džp͘ iol͘ Med͘ 77͕ 358ʹ3ϲ2͘

assel͕ S͘>͕͘ JolLJ͕ S͕͘ and SuƩerǁala͕ &͘S͘ (2ϬϬ9Ϳ͘ dhe E>ZW3 inŇammasome͗ a sensor of immune danger signals͘ Semin͘ /mmunol͘ 21͕ 194ʹ198͘

asson͕ ͘E͕͘ openhaver͕ ͘M͕͘ ǁacŬ͕ ͕͘͘ EguLJen͕ ,͘d͕͘ Stroǁig͕ d͕͘ Javdan͕ ͕͘ radleLJ͕ t͘W͕͘ &ung͕ d͕͘͘ &lavell͕ Z͕͘͘ rodsŬLJ͕ /͕͘͘ et al͘ (2Ϭ13Ϳ͘ aspase-11 acƟvaƟon in response to bacte-rial secreƟon sLJstems that access the host cLJtosol͘ W>oS Wathog͘ 9͕ e1ϬϬ34ϬϬ͘

aLJrol͕ ͕͘ and 'irard͕ J͘-W͘ (2ϬϬ9Ϳ͘ dhe />-1-liŬe cLJtoŬine />-33 is inacƟvated aŌer maturaƟon bLJ caspase-1͘ Wroc͘ Eatl͘ cad͘ Sci͘ U͘ S͘ ͘ 1Ϭϲ͕ 9Ϭ21ʹ9Ϭ2ϲ͘

hao͕ z͕͘ ShionjaŬi͕ ͘E͕͘ Srinivasula͕ S͘M͕͘ Zigoƫ͕ ͘J͕͘ &airman͕ Z͕͘ and Shi͕ z͘ (2ϬϬ5Ϳ͘ ngineering a dimeric caspase-9͗ a re-evaluaƟon of the induced prodžimitLJ model for caspase acƟvaƟon͘ W>oS iol͘ 3͕ e183͘

havarrşa-Smith͕ J͕͘ and sance͕ Z͘͘ (2Ϭ13Ϳ͘ irect proteolLJƟc cleavage of E>ZW1 is necessarLJ and suĸcient for inŇammasome acƟvaƟon bLJ anthradž lethal factor͘ W>oS Wathog͘ 9͕ e1ϬϬ3452͘ havarrşa-Smith͕ J͕͘ and sance͕ Z͘͘ (2Ϭ15Ϳ͘ dhe E>ZW1 inŇammasomes͘ /mmunol͘ Zev͘ 2ϲ5͕ 22ʹ

34͘

hĄvenj-'alĄn͕ >͕͘ renas-el ngel͕ M͕͘͘ enteno͕ ͕͘ hĄvenj͕ Z͕͘ and >ascurain͕ Z͘ (2ϬϬ9Ϳ͘ ell death mechanisms induced bLJ cLJtotodžic lLJmphocLJtes͘ ell͘ Mol͘ /mmunol͘ ϲ͕ 15ʹ25͘

hen͕ '͘z͕͘ >iu͕ M͕͘ tang͕ &͕͘ erƟn͕ J͕͘ and EƷŹenj͕ '͘ (2Ϭ11Ϳ͘  funcƟonal role for Elrpϲ in intes-Ɵnal inŇammaƟon and tumorigenesis͘ J͘ /mmunol͘ 18ϲ͕ 7187ʹ7194͘

hen͕ /͘-&͕͘ Ku-zang͕ &͕͘ ,ung͕ J͘-z͕͘ >iu͕ J͘-͕͘ tang͕ ,͕͘ tang͕ S͘-͕͘ ,ou͕ M͘-&͕͘ ,ortobagLJi͕ '͘E͕͘ and ,ung͕ M͘-͘ (2ϬϬϲͿ͘ /M2 suppresses human breast cancer cell proliferaƟon in vitro and mammarLJ tumor groǁth in a mouse model͘ Mol͘ ancer dher͘ 5͕ 1ʹ7͘

hen͕ <͘t͕͘ 'roƘ͕ ͘J͕͘ SotomaLJor͕ &͘s͕͘ StaceLJ͕ <͘J͕͘ dschopp͕ J͕͘ Sǁeet͕ M͘J͕͘ and Schroder͕ <͘ (2Ϭ14Ϳ͘ dhe neutrophil E>Z4 inŇammasome selecƟvelLJ promotes />-1ɴ maturaƟon ǁithout pLJroptosis during acute Salmonella challenge͘ ell Zep͘ 8͕ 57Ϭʹ582͘

hirivi͕ Z͘'͕͘ 'arofalo͕ ͕͘ Wadura͕ /͘M͕͘ Mantovani͕ ͕͘ and 'iavanjnji͕ Z͘ (1993Ϳ͘ /nterleuŬin 1 re-ceptor antagonist inhibits the augmentaƟon of metastasis induced bLJ interleuŬin 1 or lipo-polLJsaccharide in a human melanomaͬnude mouse sLJstem͘ ancer Zes͘ 53͕ 5Ϭ51ʹ5Ϭ54͘ ho͕ ͕͘ <im͕ d͘'͕͘ >ee͕ t͕͘ ,ǁang͕ z͘/͕͘ ho͕ ,͘/͕͘ ,an͕ ,͕͘ <ǁon͕ K͕͘ <im͕ ͕͘ WarŬ͕ ,͕͘ and ,ouh͕ ͘

(2ϬϬϬͿ͘ /nterleuŬin-18 and the cosƟmulatorLJ molecule 7-1 have a sLJnergisƟc anƟ-tumor ef-fect on murine melanoma͖ implicaƟon of combined immunotherapLJ for poorlLJ immunogenic malignancLJ͘ J͘ /nvest͘ ermatol͘ 114͕ 928ʹ934͘

hoǁ͕ M͘d͕͘ SceneaLJ͕ J͕͘ Waget͕ ͕͘ tong͕ ͘S͘&͕͘ uret͕ ,͕͘ dschopp͕ J͕͘ MƂller͕ ͕͘ and SmLJth͕ M͘J͘ (2Ϭ12Ϳ͘ E>ZW3 suppresses E< cell-mediated responses to carcinogen-induced tumors and me-tastases͘ ancer Zes͘ 72͕ 5721ʹ5732͘

hung͕ z͕͘ hang͕ S͘,͕͘ MarƟnenj͕ '͘J͕͘ zang͕ y͘K͕͘ Eurieva͕ Z͕͘ <ang͕ ,͘S͕͘ Ma͕ <͕͘ tatoǁich͕ S͘S͕͘ JeƩen͕ ͘M͕͘ dian͕ Y͕͘ ong͕ ͘ (2ϬϬ9Ϳ riƟcal ZegulaƟon of arlLJ dh17 ell iīerenƟaƟon bLJ

144 -/nterleuŬin-1 Signaling͘ /mmunitLJ 3Ϭ͕ 4͕ 57ϲ-587͘

hreƟen͕ ͘-S͕͘ >e ZoLJ͕ ͕͘ seLJ͕ E͕͘ Wrebet͕ d͕͘ laise͕ ͕͘ &auriat͕ ͕͘ and Klive͕ ͘ (2Ϭ14Ϳ͘ ancer-/n-duced lteraƟons of E<-Mediated darget ZecogniƟon͗ urrent and /nvesƟgaƟonal Wharmaco-logical Strategies iming at Zestoring E<-Mediated nƟ-dumor cƟvitLJ͘ &ront͘ /mmunol͘ 5͕ 122͘

oca͕ S͕͘ Werenj-WiƋueras͕ J͕͘ MarƟnenj͕ ͕͘ olmenareũo͕ ͕͘ Saenj͕ M͕͘͘ salleũo͕ ͕͘ Martos͕ J͕͘͘ and Moreno͕ M͘ (1997Ϳ͘ dhe prognosƟc signiĮcance of intratumoral natural Ŭiller cells in paƟents ǁith colorectal carcinoma͘ ancer 79͕ 232Ϭʹ2328͘

ooŬson͕ ͘d͕͘ and rennan͕ M͘͘ (2ϬϬ1Ϳ͘ Wro-inŇammatorLJ programmed cell death͘ drends Mi-crobiol͘ 9͕ 113ʹ114͘

ordoba-Zodriguenj͕ Z͕͘ &ang͕ ,͕͘ >anŬford͕ ͘S͘Z͕͘ and &rucht͕ ͘M͘ (2ϬϬ4Ϳ͘ nthradž lethal todžin rapidlLJ acƟvates caspase-1ͬ/ and induces edžtracellular release of interleuŬin (/>Ϳ-1beta and />-18͘ J͘ iol͘ hem͘ 279͕ 2Ϭ5ϲ3ʹ2Ϭ5ϲϲ͘

osman͕ ͕͘ Mƺllberg͕ J͕͘ Sutherland͕ ͘>͕͘ hin͕ t͕͘ rmitage͕ Z͕͘ &ansloǁ͕ t͕͘ <ubin͕ M͕͘ and halupnLJ͕ E͘J͘ (2ϬϬ1Ϳ͘ U>Ws͕ novel M, class /-related molecules͕ bind to Ms glLJcoprotein U>1ϲ and sƟmulate E< cLJtotodžicitLJ through the E<'2 receptor͘ /mmunitLJ 14͕ 123ʹ133͘ oussens͕ >͘M͕͘ and terb͕ ͘ (2ϬϬ2Ϳ͘ /nŇammaƟon and cancer͘ Eature 42Ϭ͕ 8ϲϬʹ8ϲ7͘

ounjin-&ranŬel͕ J͘ (2Ϭ13Ϳ͘ reaŬthrough of the LJear 2Ϭ13͘ ancer immunotherapLJ͘ Science 342͕ 1432ʹ1433͘

oveneLJ͕ ͕͘ theatleLJ͕ '͘,͕͘ and >LJerlLJ͕ ,͘<͘ (1997Ϳ͘ cƟve immuninjaƟon using dendriƟc cells midžed ǁith tumor cells inhibits the groǁth of primarLJ breast cancer͘ SurgerLJ 122͕ 228ʹ234͘ remer͕ /͕͘ &ridman͕ t͘,͕͘ and Sautès-&ridman͕ ͘ (2Ϭ12Ϳ͘ dumor microenvironment in ES>

suppresses E< cells funcƟon͘ KncoimmunologLJ 1͕ 244ʹ24ϲ͘

roci͕ S͕͘ Eanni͕ W͕͘ Walladini͕ ͕͘ Eicoleƫ͕ '͕͘ 'rosso͕ s͕͘ enegiamo͕ '͕͘ >andunjnji͕ >͕͘ >amolinara͕ ͕͘ /annjano͕ M͘>͕͘ Zanieri͕ ͕͘ et al͘ (2Ϭ15Ϳ͘ /nterleuŬin-15 is reƋuired for immunosurveillance and immunoprevenƟon of ,Z2ͬneu-driven mammarLJ carcinogenesis͘ reast ancer Zes͘ 17͕ 7Ϭ͘

ullen͕ S͘W͕͘ <earneLJ͕ ͘J͕͘ lancLJ͕ ͘M͕͘ and MarƟn͕ S͘J͘ (2Ϭ15Ϳ͘ iverse cƟvators of the E>ZW3 /nŇammasome Wromote />-1ɴ SecreƟon bLJ driggering Eecrosis͘ ell Zep͘ 11͕ 1535ʹ1548͘

D

EK/y͕ W͘&͘ (1953Ϳ͘ ΀Eomenclature and classiĮcaƟon of cancers based on an atlas΁͘ cta Unio /nt͘ ontra ancrum 9͕ 7ϲ9ʹ771͘

van eventer͕ ,͘t͕͘ urgents͕ J͕͘͘ tu͕ Y͘W͕͘ toodford͕ Z͘-M͘d͕͘ ricŬeLJ͕ t͘J͕͘ llen͕ /͕͘͘ Mclva-nia-deŬippe͕ ͕͘ SerodLJ͕ J͘S͕͘ and ding͕ J͘W͘-z͘ (2Ϭ1ϬͿ͘ dhe inŇammasome component E>ZW3 im-pairs anƟtumor vaccine bLJ enhancing the accumulaƟon of tumor-associated mLJeloid-derived suppressor cells͘ ancer Zes͘ 7Ϭ͕ 1Ϭ1ϲ1ʹ1Ϭ1ϲ9͘

eǁan͕ M͕͘͘ derunuma͕ ,͕͘ hmed͕ S͕͘ Khba͕ <͕͘ daŬada͕ M͕͘ danaŬa͕ z͕͘ doi͕ M͕͘ and zamamoto͕ E͘ (2ϬϬ5Ϳ͘ Eatural Ŭiller cells in breast cancer cell groǁth and metastasis in S/ mice͘ io-med͘ Wharmacother͘ с iomédecine Wharmacothérapie 59 Suppl 2͕ S375ʹS379͘

eǁan͕ M͕͘͘ derunuma͕ ,͕͘ daŬada͕ M͕͘ danaŬa͕ z͕͘ be͕ ,͕͘ Sata͕ d͕͘ doi͕ M͕͘ and zamamoto͕ E͘ (2ϬϬ7Ϳ͘ Zole of natural Ŭiller cells in hormone-independent rapid tumor formaƟon and spon-taneous metastasis of breast cancer cells in vivo͘ reast ancer Zes͘ dreat͘ 1Ϭ4͕ 2ϲ7ʹ275͘

ianj͕ E͕͘ Minton͕ S͕͘ odž͕ ͕͘ oǁman͕ d͕͘ 'ritsŬo͕ d͕͘ 'arcia͕ Z͕͘ ǁeis͕ /͕͘ tloch͕ M͕͘ >ivingston͕ S͕͘ Seiũo͕ ͕͘ et al͘ (2ϬϬϲͿ͘ cƟvaƟon of stat3 in primarLJ tumors from high-risŬ breast cancer pa-Ɵents is associated ǁith elevated levels of acƟvated SZ and survivin edžpression͘ lin͘ ancer Zes͘ 12͕ 2Ϭʹ28͘

inarello͕ ͘͘ (1991Ϳ͘ /nterleuŬin-1 and interleuŬin-1 antagonism͘ lood 77͕ 1ϲ27ʹ1ϲ52͘

inarello͕ ͘͘ (2ϬϬ9Ϳ͘ /mmunological and inŇammatorLJ funcƟons of the interleuŬin-1 familLJ͘ nnu͘ Zev͘ /mmunol͘ 27͕ 519ʹ55Ϭ͘

inarello͕ ͕͘͘ and van der Meer͕ J͘t͘M͘ (2Ϭ13Ϳ͘ dreaƟng inŇammaƟon bLJ blocŬing interleuŬin-1 in humans͘ Semin͘ /mmunol͘ 25͕ 4ϲ9ʹ484͘

irat͕ ͕͘ ochet͕ >͕͘ abeŬ͕ M͕͘ aviaud͕ ͕͘ auvillier͕ S͕͘ Maũed͕ ͕͘ tang͕ z͘z͕͘ Meulle͕ ͕͘ Salles͕ ͕͘ >e 'onidec͕ S͕͘ et al͘ (2Ϭ11Ϳ͘ ancer-associated adipocLJtes edžhibit an acƟvated phenotLJpe and contribute to breast cancer invasion͘ ancer Zes͘ 71͕ 2455ʹ24ϲ5͘

ostert͕ ͕͘ Wétrilli͕ s͕͘ san ruggen͕ Z͕͘ Steele͕ ͕͘ Mossman͕ ͘d͕͘ and dschopp͕ J͘ (2ϬϬ8Ϳ͘ /nnate immune acƟvaƟon through Ealp3 inŇammasome sensing of asbestos and silica͘ Science 32Ϭ͕ ϲ74ʹϲ77͘

oǁds͕ d͕͘͘ Masumoto͕ J͕͘ hu͕ >͕͘ /nohara͕ E͕͘ and EƷŹenj͕ '͘ (2ϬϬ4Ϳ͘ rLJopLJrinduced in-terleuŬin 1beta secreƟon in monocLJƟc cells͗ enhanced acƟvitLJ of disease-associated mutants and reƋuirement for S͘ J͘ iol͘ hem͘ 279͕ 21924ʹ21928͘

rummond͕ Z͕͘͘ Saiũo͕ S͕͘ /ǁaŬura͕ z͕͘ and roǁn͕ '͘͘ (2Ϭ11Ϳ͘ dhe role of SLJŬͬZ9 coupled -tLJpe lecƟns in anƟfungal immunitLJ͘ ur͘ J͘ /mmunol͘ 41͕ 27ϲʹ281͘

u͕ Y͕͘ tang͕ Y͕͘ &an͕ ,͕͘ tang͕ J͕͘ >iu͕ y͕͘ tang͕ ,͕͘ tang͕ z͕͘ and ,u͕ Z͘ (2Ϭ1ϲͿ͘ ietarLJ choles-terol promotes KM-induced colorectal cancer through acƟvaƟng the E>ZW3 inŇammasome͘ iochem͘ Wharmacol͘ 1Ϭ5͕ 42ʹ54͘

u͕ Z͕͘ >u͕ <͘ s͕ Wetritsch͕ ͕͘ >iu͕ W͕͘ 'anss͕ Z͕͘ Wassegué͕ ͕͘ Song͕ ,͕͘ sandenberg͕ S͕͘ Johnson͕ Z͘S͕͘ terb͕ ͕͘ et al͘ (2ϬϬ8Ϳ͘ ,/&1alpha induces the recruitment of bone marroǁ-derived vas-cular modulatorLJ cells to regulate tumor angiogenesis and invasion͘ ancer ell 13͕ 2Ϭϲʹ22Ϭ͘ ueǁell͕ W͕͘ <ono͕ ,͕͘ ZaLJner͕ <͘J͕͘ Sirois͕ ͘M͕͘ sladimer͕ '͕͘ auernfeind͕ &͘'͕͘ bela͕ '͘S͕͘ &ranchi͕

>͕͘ EuŹenj͕ '͕͘ Schnurr͕ M͕͘ et al͘ (2Ϭ1ϬͿ͘ E>ZW3 inŇammasomes are reƋuired for atherogenesis and acƟvated bLJ cholesterol crLJstals͘ Eature 4ϲ4͕ 1357ʹ13ϲ1͘

unn͕ '͘W͕͘ Kld͕ >͘J͕͘ and Schreiber͕ Z͘͘ (2ϬϬ4Ϳ͘ dhe immunobiologLJ of cancer immunosurveil-lance and immunoediƟng͘ /mmunitLJ 21͕ 137ʹ148͘

upaul-hicoine͕ J͕͘ rabnjadeh͕ ͕͘ agenais͕ M͕͘ ouglas͕ d͕͘ hampagne͕ ͕͘ Morinjot͕ ͕͘ Zo-drigue-'ervais͕ /͘'͕͘ reton͕ s͕͘ olpiƩs͕ S͘>͕͘ eauchemin͕ E͕͘ et al͘ (2Ϭ15Ϳ͘ dhe Elrp3 /nŇam-masome Suppresses olorectal ancer MetastaƟc 'roǁth in the >iver bLJ WromoƟng Eatural <iller ell dumoricidal cƟvitLJ͘ /mmunitLJ 43͕ 751ʹ7ϲ3͘

uWre͕͛ S͕͘͘ and ,unter͕ <͘t͘ (2ϬϬ7Ϳ͘ Murine mammarLJ carcinoma 4d1 induces a leuŬemoid reacƟon ǁith splenomegalLJ͗ associaƟon ǁith tumor-derived groǁth factors͘ džp͘ Mol͘ Wathol͘ 82͕ 12ʹ24͘

E

dgeǁorth͕ J͕͘͘ Spencer͕ J͕͘ Whalipon͕ ͕͘ 'riĸn͕ '͕͘͘ and Sansoneƫ͕ W͘J͘ (2ϬϬ2Ϳ͘ LJtotodžicitLJ and interleuŬin-1beta processing folloǁing Shigella Ňedžneri infecƟon of human monocLJte-de-rived dendriƟc cells͘ ur͘ J͘ /mmunol͘ 32͕ 14ϲ4ʹ1471͘

14ϲ

-linav͕ ͕͘ Stroǁig͕ d͕͘ ,enao-Meũia͕ J͕͘ and &lavell͕ Z͘͘ (2Ϭ11aͿ͘ ZegulaƟon of the anƟmicrobial response bLJ E>Z proteins͘ /mmunitLJ 34͕ ϲϲ5ʹϲ79͘

linav͕ ͕͘ Stroǁig͕ d͕͘ <au͕ ͘>͕͘ ,enao-Meũia͕ J͕͘ dhaiss͕ ͕͘͘ ooth͕ ͘J͕͘ Weaper͕ ͘Z͕͘ erƟn͕ J͕͘ isenbarth͕ S͕͘͘ 'ordon͕ J͘/͕͘ et al͘ (2Ϭ11bͿ͘ E>ZWϲ inŇammasome regulates colonic microbial ecologLJ and risŬ for coliƟs͘ ell 145͕ 745ʹ757͘

lŬabets͕ M͕͘ Zibeiro͕ s͘S͘'͕͘ inarello͕ ͕͘͘ Kstrand-Zosenberg͕ S͕͘ i Santo͕ J͘W͕͘ pte͕ Z͘E͕͘ and sosshenrich͕ ͘͘J͘ (2Ϭ1ϬͿ͘ />-1ɴ regulates a novel mLJeloid-derived suppressor cell subset that impairs E< cell development and funcƟon͘ ur͘ J͘ /mmunol͘ 4Ϭ͕ 3347ʹ3357͘

mens͕ >͘͘ (2Ϭ12Ϳ͘ reast cancer immunobiologLJ driving immunotherapLJ͗ vaccines and immune checŬpoint blocŬade͘ džpert Zev͘ nƟcancer dher͘ 12͕ 1597ʹ1ϲ11͘

rcan͕ ͕͘ van iest͕ W͘J͕͘ van der nde͕ ͕͘ ,inrichs͕ J͕͘ ult͕ W͕͘ uerger͕ ,͕͘ van der tall͕ ͕͘ and erŬsen͕ W͘t͘͘ (2Ϭ12Ϳ͘ p53 mutaƟons in classic and pleomorphic invasive lobular carcinoma of the breast͘ ell͘ Kncol͘ (ordrͿ͘ 35͕ 111ʹ118͘

rener͕ S͕͘ Wétrilli͕ s͕͘ <assner͕ /͕͘ Minoƫ͕ Z͕͘ asƟllo͕ Z͕͘ Santoro͕ Z͕͘ ,assa͕ W͘K͕͘ dschopp͕ J͕͘ and ,oƫger͕ M͘K͘ (2Ϭ12Ϳ͘ /nŇammasome-acƟvated caspase 7 cleaves WZW1 to enhance the edž-pression of a subset of E&-ʃ target genes͘ Mol͘ ell 4ϲ͕ 2ϬϬʹ211͘

F

&abbi͕ M͕͘ arboƫ͕ '͕͘ and &errini͕ S͘ (2Ϭ15Ϳ͘ ontedžt-dependent role of />-18 in cancer biologLJ and counter-regulaƟon bLJ />-18W͘ J͘ >euŬoc͘ iol͘ 97͕ ϲϲ5ʹϲ75͘

&ausƟn͕ ͕͘ >arƟgue͕ >͕͘ rueLJ͕ J͘-M͕͘ >uciano͕ &͕͘ SergienŬo͕ ͕͘ aillLJ-Maitre͕ ͕͘ solŬmann͕ E͕͘ ,anein͕ ͕͘ Zouiller͕ /͕͘ and Zeed͕ J͘͘ (2ϬϬ7Ϳ͘ ZeconsƟtuted E>W1 inŇammasome reveals tǁo-step mechanism of caspase-1 acƟvaƟon͘ Mol͘ ell 25͕ 713ʹ724͘

&erlaLJ͕ J͕͘ Soerũomataram͕ /͕͘ iŬshit͕ Z͕͘ ser͕ S͕͘ Mathers͕ ͕͘ Zebelo͕ M͕͘ WarŬin͕ ͘M͕͘ &orman͕ ͕͘ and raLJ͕ &͘ (2Ϭ15Ϳ͘ ancer incidence and mortalitLJ ǁorldǁide͗ sources͕ methods and maũor