瀵艱錛?/strong>鍏嶇柅媯�鏌ョ偣闃繪柇錛圛CB錛変負(fù)娌葷枟鑳冪檶錛圙.C.錛夋彁渚涗簡鏂扮殑鏈轟細(xì)銆備簡瑙ｅ厤鐤鏌ョ偣鐨勪笂娓歌皟鎺у浜庤繘涓�姝ユ彁楂業(yè)CB娌葷枟鐨勭枟鏁堣嚦鍏抽噸瑕併�?/p>
6鏈?6鏃ワ紝鍖椾含澶у鑲跨槫鍖婚櫌瀛ｅ姞瀛氭暀鎺堝洟闃熷湪銆奡ignal Transduction and Targeted Therapy銆嬩笂鍙戣〃棰樹負(fù)鈥淭RIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance鈥濈殑鐮旂┒璁烘枃錛?strong style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important; visibility: visible;">鐮旂┒琛ㄦ槑TBK1鎶戝埗鍓備笌CTLA4鍏嶇柅媯�鏌ョ偣闃繪柇鑱斿悎浣跨敤瀵笹.C.鍏鋒湁鍗忓悓浣滅敤錛屼負(fù)G.C.娌葷枟鎻愪緵浜嗕竴縐嶆柊鐨勭瓥鐣ャ�?/strong> https://www.nature.com/articles/s41392-023-01450-3 鐮旂┒鑳屾櫙 01 灝界鑳冪檶錛圙.C.錛夌殑鍙戠梾鐜囧拰鐩稿叧姝諱骸鐜囩戶緇笅闄嶏紝浣?2020 騫村叏鐞冩湁 1錛?89錛?03 浜鴻璇婃柇鎮(zhèn)ｆ湁鑳冪檶;綰︽湁768錛?93浜烘浜★紝浣垮叾鎴愪負(fù)褰撳勾鐧岀棁鐩稿叧姝諱骸鐨勭涓夊ぇ鍘熷洜銆傝繖浜涚梾渚嬩腑綰︽湁44%錛?78錛?08渚嬶級鏉ヨ嚜涓浗銆傝瘑鍒厤鐤鏌ョ偣錛圛.C.錛夊拰寮�鍙慖.C.鎶戝埗鍓傦紙ICI錛夊凡緇忓交搴曟敼鍙樹簡鐧岀棁娌葷枟銆傞樆鏂璓D-1 / PD-L1閫氳礬鐨勫厤鐤枟娉曟渶榪戝凡琚敤浜嶨.C.娌葷枟銆傚笗鍗氬埄鐝犲崟鎶楋紙Keytruda錛夋槸涓�縐嶄漢婧愬寲鎶椾綋錛屽凡琚壒鍑嗙敤浜庤〃杈綪D-L1鐨勫鍙戞�у眬閮ㄦ櫄鏈熸垨杞Щ鎬ц儍鎴栬儍椋熺浜ょ晫澶勶紙GEJ錛夎吅鐧屾?zhèn)ｈ�呯殑鍏嶇柅娌葷枟銆傝秺鏉ヨ秺澶氱殑璇佹嵁琛ㄦ槑錛孭D-L1鏄‘瀹氬厤鐤不鐤楃枟鏁堢殑閲嶈鐢熺墿鏍囧織鐗┿�傚洜姝わ紝浜嗚В璋冩帶PD-L1鍦℅.C.緇嗚優(yōu)涓〃杈懼拰/鎴栫ǔ瀹氭�х殑鍒嗗瓙鏈哄埗灝嗕負(fù)鏀瑰杽鍏嶇柅鐤楁硶鐨勪復(fù)搴婂弽搴旀彁渚涘垎瀛愯瘉鎹�?/strong> 鐮旂┒榪涘睍 02 涓轟簡鎵懼埌璋冭妭G.C涓璓D-L1琛ㄨ揪鐨勫熀鍥狅紝鎴戜滑鍦∟9鑳冪檶緇嗚優(yōu)緋諱腑榪涜浜嗗熀浜庡叏鍩哄洜緇凜RISPR-Cas87鐨勭瓫閫夈�傜粏鑳?yōu)鎰熸煋鍚湁鍚戝RNA錛坓RNA錛夌殑鎱㈢梾姣掞紝騫剁敤鍢屽懁闇夌礌榪涜閫夋嫨銆傛牴鎹甈D-L1琛ㄨ揪瀵硅漿瀵肩粏鑳?yōu)杩涜鍒嗛�夛紝騫惰繘琛屾繁搴︽祴搴忓垎鏋愩�傞殢鍚庯紝鎴戜滑浣跨敤MAGeCK綆楁硶閫氳繃璁＄畻姣忎釜鍩哄洜鐨勎茶瘎鍒嗗璐熸垨姝ｈ皟鑺侾D-L1琛ㄨ揪鐨勫熀鍥犺繘琛岃瘎鍒嗐�傚湪鎴戜滑鐨勭粨鏋滀腑錛?strong style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important;">浣滀負(fù)PD-L1琛ㄨ揪鐨勫凡鐭ヨ皟鑺傚洜瀛愮殑鍩哄洜錛屽CD274錛孖RF2錛孲TAT3鍜孖RF1錛岃璐熸�ч�夋嫨錛岀‘璁や簡鎴戜滑絳涢�夌郴緇熺殑鏁堢巼鍜岀簿搴?/strong>銆傛澶栵紝TRIM28浣嶄簬璋冭妭PD-L300紼沖畾鎬х殑1涓鍚戦�夋嫨鍩哄洜鐨勯《閮ㄣ�備負(fù)浜嗛獙璇佽繖涓�瑙傚療緇撴灉錛屾垜浠繘琛屼簡CRISPR-Cas1浠嬪鐨凾RIM9鏁查櫎錛?strong style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important;">緇撴灉琛ㄦ槑TRIM28鐨勭己澶辨樉钁楅檷浣庝簡G.C.緇嗚優(yōu)涓璓D-L28鐨勮〃杈俱�?/strong> 鎺ヤ笅鏉ワ紝鎴戜滑鐮旂┒浜員RIM28鍜孭D-L1琛ㄨ揪涔嬮棿鐨勭浉鍏蟲�с�傞鍏堬紝鎴戜滑媯�嫻嬩簡TRIM28鍦ㄥ涓狦.C.緇嗚優(yōu)緋諱腑鐨勫熀鏈〃杈炬按騫熾�傛垜浠皟鑺備簡涓嶅悓G.C.緇嗚優(yōu)緋諱腑鐨凾RIM28琛ㄨ揪銆傜粨鏋滆〃鏄庯紝TRIM28榪囪〃杈炬樉钁楁彁楂樹簡SGC-7901鍜孧GC-803緇嗚優(yōu)涓璓D-L1铔嬬櫧姘村鉤錛岃�孴RIM28鍘婚櫎闄嶄綆浜咥GS鍜孊GC-823緇嗚優(yōu)涓璓D-L1琛ㄨ揪錛岃〃鏄嶵RIM28姝ｅ悜璋冭妭G.C.緇嗚優(yōu)涓璓D-L1鐨勮〃杈俱�?/strong>鎹姤閬擄紝PD-L1寰堝鏄撶粡鍘嗙炕璇戝悗淇グ;鍥犳錛屾垜浠繘涓�姝ョ爺絀朵簡TRIM28鏄惁鐩存帴璋冭妭PD-L1铔嬬櫧紼沖畾鎬с�傜粨鏋滆〃鏄庯紝TRIM28鐨勮�楃鏄捐憲緙╃煭浜哖D-L1鐨勫崐琛版湡錛岃〃鏄嶵RIM28紼沖畾浜咷.C.緇嗚優(yōu)涓殑PD-L1铔嬬櫧銆傛湁瓚ｇ殑鏄紝鎴戜滑瑙傚療鍒癟RIM28榪樺彲浠ヤ笂璋働D-L1 mRNA姘村鉤錛岃〃鏄嶵RIM28鍙兘瀵筆D-L1鐨刴RNA鍜岃泲鐧借川姘村鉤閮芥湁璋冭妭浣滅敤銆?/strong> 鐮旂┒緇撹 03 鐮旂┒涓紝鎴戜滑鍦∟87鑳冪檶緇嗚優(yōu)緋諱腑榪涜浜嗗熀浜嶧ACS鐨勫叏鍩哄洜緇凜RISPR-Cas9絳涢�夈�備嬌鐢∕AGeCK鍒嗘瀽騫舵瘮杈冧簡PD-L1浣庝簹緹ゅ拰楂楶D-L1浜氱兢涔嬮棿鐨剆gRNA涓板害銆傛垜浠殑絳涢�夌‘瀹歍RIM28錛屼篃縐頒負(fù)TIF1尾鍜孠AP1錛屾槸PD-L1鐨勯《綰у亣瀹氳皟鑺傚洜瀛愪箣涓�銆傛垜浠繘琛屼簡鍑犻」鐢熷寲鍒嗘瀽錛屼互闃愭槑TRIM28瀵笹.C.緇嗚優(yōu)涓璓D-L1紼沖畾鎬у拰琛ㄨ揪鐨勫獎鍝嶃�備負(fù)浜嗙爺絀禩RIM28鑰楃鎴栬繃琛ㄨ揪瀵笹.C.緇嗚優(yōu)涓叏灞�鍩哄洜琛ㄨ揪鐨勫獎鍝嶏紝榪涜浜哛NA-seq銆傚埄鐢ㄧ患鍚堢敓鐗╀俊鎭鍒嗘瀽錛屽皬榧犳ā鍨嬪拰涓村簥瑙傚療錛屾垜浠瘯鍥炬彮紺篢RIM28浠嬪鐨凱D-L1涓婅皟瀵硅偪鐦ょ敓闀垮拰鎶楄偪鐦ゅ厤鐤殑褰卞搷銆?/p> 鎬諱箣錛?strong style="margin: 0px; padding: 0px; outline: 0px; max-width: 100%; box-sizing: border-box !important; overflow-wrap: break-word !important;">鎴戜滑鐨勭爺絀朵笉浠呮彮紺轟簡涓�縐嶈皟鑺侾D-L1琛ㄨ揪鍜岀ǔ瀹氭�х殑鏂版満鍒訛紝鑰屼笖榪樺己璋冧簡浣跨敤TBK1鎶戝埗鍓備笌CTLA4鍏嶇柅媯�鏌ョ偣闃繪柇鑱斿悎娌葷枟G.C.鐨勬綔鍦ㄧ瓥鐣ャ�?/strong> 鍙傝�冭祫鏂欙細(xì)https://www.nature.com/articles/s41392-023-01450-3
