{"id":3595,"date":"2024-06-09T07:00:16","date_gmt":"2024-06-08T23:00:16","guid":{"rendered":"http:\/\/oncolab.cn\/index.php\/2024\/06\/09\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac29%e7%ab%a0-%e5%87%8f%e5%b0%91%e8%82%bf%e7%98%a4%e5%86%85%e8%b0%83%e8%8a%82%e6%80%a7t%e7%bb%86%e8%83%9e%e7%9a%84%e7%ad%96%e7%95%a5%ef%bc%88-2\/"},"modified":"2024-06-09T07:00:16","modified_gmt":"2024-06-08T23:00:16","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac29%e7%ab%a0-%e5%87%8f%e5%b0%91%e8%82%bf%e7%98%a4%e5%86%85%e8%b0%83%e8%8a%82%e6%80%a7t%e7%bb%86%e8%83%9e%e7%9a%84%e7%ad%96%e7%95%a5%ef%bc%88-2","status":"publish","type":"post","link":"http:\/\/oncolab.cn\/index.php\/2024\/06\/09\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac29%e7%ab%a0-%e5%87%8f%e5%b0%91%e8%82%bf%e7%98%a4%e5%86%85%e8%b0%83%e8%8a%82%e6%80%a7t%e7%bb%86%e8%83%9e%e7%9a%84%e7%ad%96%e7%95%a5%ef%bc%88-2\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c29\u7ae0 \u51cf\u5c11\u80bf\u7624\u5185\u8c03\u8282\u6027T\u7ec6\u80de\u7684\u7b56\u7565\uff08\u4e0b\uff09"},"content":{"rendered":"
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\u4e0a\u671f\u5185\u5bb9\uff1a\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c29\u7ae0 \u51cf\u5c11\u80bf\u7624\u5185\u8c03\u8282\u6027T\u7ec6\u80de\u7684\u7b56\u7565\uff08\u4e0a\uff09<\/span><\/a><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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29.5 \u9488\u5bf9Treg\u7684\u6297\u8840\u7ba1\u751f\u6210\u7597\u6cd5<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u8840\u7ba1\u5185\u76ae\u751f\u957f\u56e0\u5b50-A\uff08VEGF-A\uff09\u5728\u80bf\u7624\u8bf1\u5bfc\u7684\u514d\u75ab\u6291\u5236\u4e2d\u626e\u6f14\u5173\u952e\u89d2\u8272\uff0c\u5c24\u5176\u662f\u5728Treg\u7684\u79ef\u805a\u65b9\u9762\u3002\u5728\u80bf\u7624\u643a\u5e26\u5bbf\u4e3b\u4e2d\uff0cVEGF-A\u4e0d\u4ec5\u53ef\u4ee5\u963b\u65ad\u6811\u7a81\u72b6\u7ec6\u80de\uff08DC\uff09\u7684\u6210\u719f\uff0c\u8fd8\u53ef\u4ee5\u589e\u52a0\u9ad3\u7cfb\u6291\u5236\u7ec6\u80de\uff08MDSC\uff09\u7684\u6bd4\u4f8b\u3002\u8fd9\u4e24\u79cd\u7ec6\u80de\u7c7b\u578b\u90fd\u53ef\u80fd\u53c2\u4e0eTreg\u7684\u589e\u6b96\u6216\u662f\u4f20\u7edfT\u7ec6\u80de\uff08Tconv\uff09\u5411Treg\u7684\u8f6c\u5316\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u80bf\u7624\u643a\u5e26\u7684\u5c0f\u9f20\u53ca\u4eba\u7c7b\u80bf\u7624\u7684DC\u7ec6\u80de\u8868\u9762\u6709VEGF-A\u53d7\u4f53\u7684\u8868\u8fbe\uff0c\u8bf4\u660eVEGF-A\u5bf9DC\u5177\u6709\u76f4\u63a5\u5f71\u54cd\u3002\u5b9e\u9645\u4e0a\uff0c\u6765\u81ea\u80bf\u7624\u7684VEGF-A\u5728\u8377\u7624\u5c0f\u9f20\u548c\u8f6c\u79fb\u6027\u764c\u75c7\u60a3\u8005\u4f53\u5185\u53ef\u4ee5\u76f4\u63a5\u8bf1\u5bfcTreg\u7684\u589e\u6b96\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5f53\u524d\uff0c\u9488\u5bf9VEGF-A\/VEGF-R2\u901a\u8def\u7684\u6297\u8840\u7ba1\u751f\u6210\u7597\u6cd5\u5df2\u88ab\u5e7f\u6cdb\u5e94\u7528\u4e8e\u591a\u79cd\u764c\u75c7\u7684\u6cbb\u7597\uff0c\u5305\u62ec\u8f6c\u79fb\u6027\u7ed3\u76f4\u80a0\u764c\u3001\u8f6c\u79fb\u6027\u80be\u7ec6\u80de\u764c\u3001\u665a\u671f\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u548c\u5375\u5de2\u764c\u3002\u4f8b\u5982\uff0c\u8212\u5c3c\u66ff\u5c3c\uff0c\u4e00\u79cd\u9488\u5bf9VEGF\u53d7\u4f53\u3001PDGFR\u3001c-kit\u548cFlt3\u7684\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\uff0c\u5df2\u88ab\u8bc1\u5b9e\u80fd\u591f\u51cf\u5c11\u8f6c\u79fb\u6027\u80be\u7ec6\u80de\u764c\u60a3\u8005\u4e2dTreg\u7684\u6bd4\u4f8b\u3002\u5728\u80be\u7ec6\u80de\u764c\u548c\u809d\u7ec6\u80de\u764c\u60a3\u8005\u4e2d\uff0c\u53e6\u4e00\u79cd\u591a\u9776\u70b9\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\uff0c\u7d22\u62c9\u975e\u5c3c\uff08\u9776\u5411VEGF\u53d7\u4f53\u3001PDGFR\u3001c-kit\u3001Raf\u6fc0\u9176\u3001RET\uff09\uff0c\u4e5f\u5df2\u7ecf\u8bc1\u660e\u80fd\u5bf9Treg\u4ea7\u751f\u4e0d\u5229\u5f71\u54cd\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u8d1d\u4f10\u5355\u6297\u662f\u4e00\u79cd\u4eba\u6e90\u5316\u7684\u6297\u8840\u7ba1\u5185\u76ae\u751f\u957f\u56e0\u5b50-A\uff08VEGF-A\uff09\u5355\u514b\u9686\u6297\u4f53\uff0c\u5df2\u88ab\u8bc1\u5b9e\u80fd\u591f\u5728\u8377\u7624\u5c0f\u9f20\u548c\u8f6c\u79fb\u6027\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u4e2d\u51cf\u5c11Tregs\u7684\u6bd4\u4f8b\u548c\u6570\u91cf\u3002\u901a\u8fc7\u963b\u65adVEGF-A\/VEGF-R2\u901a\u8def\uff0c\u4e0d\u4ec5\u53ef\u4ee5\u6062\u590d\u6b63\u5e38\u7684Treg\u6bd4\u4f8b\uff0c\u8fd8\u80fd\u8c03\u8282\u80bf\u7624\u8bf1\u5bfc\u7684\u5176\u4ed6\u514d\u75ab\u9003\u9038\u673a\u5236\uff0c\u5982\u9ad3\u7cfb\u6291\u5236\u7ec6\u80de\uff08MDSC\uff09\u7684\u8bf1\u5bfc\u548cCD8+ T\u7ec6\u80de\u4e0a\u6291\u5236\u6027\u68c0\u67e5\u70b9\u7684\u8868\u8fbe\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u57fa\u4e8e\u8fd9\u4e9b\u53d1\u73b0\uff0c\u6211\u4eec\u5728\u7ed3\u76f4\u80a0\u764c\u7684\u5c0f\u9f20\u6a21\u578b\u4e2d\u8bc1\u5b9e\u4e86VEGF-A\u6297\u4f53\u80fd\u4e0e\u514d\u75ab\u6cbb\u7597\uff08\u5c24\u5176\u662f\u68c0\u67e5\u70b9\u6291\u5236\u5242\uff09\u4ea7\u751f\u534f\u540c\u6548\u5e94\u3002\u76ee\u524d\uff0c\u8fd9\u79cd\u6297\u8840\u7ba1\u751f\u6210\u7597\u6cd5\u4e0e\u514d\u75ab\u6cbb\u7597\u7684\u7ec4\u5408\u7b56\u7565\u6b63\u5728\u4e0d\u540c\u7c7b\u578b\u7684\u764c\u75c7\u4e2d\u8fdb\u884c\u8bc4\u4f30\uff0c\u5305\u62ec\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\uff08NCT02400385\uff09\u3001\u80be\u7ec6\u80de\u764c\uff08NCT02348008\uff09\u548c\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08NCT02039674\uff09\u3002\u8fd9\u4e9b\u7814\u7a76\u65e8\u5728\u6df1\u5165\u63a2\u7d22\u6297\u8840\u7ba1\u751f\u6210\u5206\u5b50\u4e0e\u514d\u75ab\u7597\u6cd5\u76f8\u7ed3\u5408\u7684\u6cbb\u7597\u6f5c\u529b\uff0c\u4ee5\u671f\u63d0\u9ad8\u6cbb\u7597\u6548\u679c\u5e76\u6539\u5584\u60a3\u8005\u7684\u9884\u540e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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29.6 \u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u7597\u6cd5(\u6297CTLA-4\u6297\u4f53)<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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CTLA-4\u662f\u4e00\u79cd\u5171\u6291\u5236\u53d7\u4f53\uff0c\u4e3b\u8981\u8868\u8fbe\u5728\u6fc0\u6d3b\u7684\u7ec6\u80de\u6bd2\u6027T\u6dcb\u5df4\u7ec6\u80de\u4e0a\uff0c\u901a\u8fc7\u6291\u5236\u514d\u75ab\u53cd\u5e94\u3001\u51cf\u5c11IL-2\u7684\u4ea7\u751f\u548c\u5f71\u54cd\u7ec6\u80de\u5468\u671f\u6765\u53d1\u6325\u4f5c\u7528\u3002\u8fd9\u79cd\u8d1f\u53cd\u9988\u673a\u5236\u5728\u591a\u79cd\u5c0f\u9f20\u6a21\u578b\u4e2d\u963b\u6b62\u4e86\u6dcb\u5df4\u589e\u6b96\u548c\u81ea\u8eab\u514d\u75ab\u53cd\u5e94\u7684\u53d1\u751f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u764c\u75c7\u6cbb\u7597\u4e2d\uff0cCTLA-4\u5728\u6548\u5e94T\u7ec6\u80de\u4e0a\u7684\u8868\u8fbe\u53ef\u80fd\u5bfc\u81f4\u5bf9\u6076\u6027\u7ec6\u80de\u7684\u53cd\u5e94\u4f4e\u4e0b\u6216\u65e0\u6548\u3002\u57fa\u4e8eCTLA-4\u7684\u8fd9\u4e00\u7279\u6027\uff0c\u5f00\u53d1\u4e86\u591a\u79cd\u6297CTLA-4\u6297\u4f53\uff0c\u5982ipilimumab\uff08IgG1\uff09\u548ctremelimumab\uff08IgG2\uff09\uff0c\u8fd9\u4e24\u79cd\u90fd\u662f\u5b8c\u6574\u7684\u4eba\u6e90\u5316\u5355\u514b\u9686\u6297\u4f53\u3002Ipilimumab\u4e8e2011\u5e74\u83b7\u5f97FDA\u6279\u51c6\uff0c\u6210\u4e3a\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684\u4e00\u7ebf\u6cbb\u7597\u9009\u9879\u3002Tremelimumab\u4e8e2015\u5e74\u88abFDA\u6279\u51c6\u7528\u4e8e\u6cbb\u7597\u6076\u6027\u95f4\u76ae\u7624\u60a3\u8005\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7136\u800c\uff0cCTLA-4\u4e5f\u5728Treg\u7ec6\u80de\u4e0a\u7ec4\u6210\u6027\u8868\u8fbe\uff0c\u5e76\u5728\u5176\u8c03\u8282\u529f\u80fd\u4e2d\u53d1\u6325\u91cd\u8981\u4f5c\u7528\u3002\u9488\u5bf9\u8fd9\u4e00\u70b9\uff0c\u79d1\u7814\u754c\u8fdb\u884c\u4e86\u591a\u9879\u4e34\u5e8a\u524d\u548c\u4e34\u5e8a\u7814\u7a76\uff0c\u4ee5\u63a2\u7a76\u6297CTLA-4\u7597\u6cd5\u5bf9Tregs\u7684\u6f5c\u5728\u5f71\u54cd\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Kavanagh\u53ca\u5176\u540c\u4e8b\u7814\u7a76\u4e86\u4e0d\u540c\u5242\u91cf\u7684ipilimumab\u5bf9\u8f6c\u79fb\u6027\u524d\u5217\u817a\u764c\u60a3\u8005\u7684\u5f71\u54cd\u3002\u4ed6\u4eec\u89c2\u5bdf\u5230\uff0c\u65e0\u8bba\u662f\u4f4e\u5242\u91cf1.5 mg\/kg\u8fd8\u662f\u66f4\u9ad8\u5242\u91cf\uff0c\u90fd\u4f1a\u8bf1\u5bfc\u5916\u5468\u8840\u4e2dCD4+<\/sup>FoxP3+<\/sup>\u529f\u80fd\u6027Tregs\u7684\u5242\u91cf\u4f9d\u8d56\u6027\u589e\u52a0\u3002\u5176\u4ed6\u7814\u7a76\u4e5f\u53d1\u73b0\u4e86\u7c7b\u4f3c\u7ed3\u679c\uff0c\u8868\u660e\u6297CTLA-4\u7597\u6cd5\u80fd\u591f\u8bf1\u5bfc\u5916\u5468Treg\u7684\u589e\u6b96\u3002\u7136\u800c\uff0c\u5916\u5468\u8840\u4e2d\u7684\u514d\u75ab\u72b6\u51b5\u5e76\u4e0d\u4e00\u5b9a\u80fd\u51c6\u786e\u53cd\u6620\u80bf\u7624\u5fae\u73af\u5883\uff08TME\uff09\u4e2d\u7684\u5b9e\u9645\u60c5\u51b5\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u4e24\u9879\u4e34\u5e8a\u524d\u7814\u7a76\u8868\u660e\uff0c\u6297CTLA-4\u5355\u6297\u80fd\u591f\u8bf1\u5bfc\u80bf\u7624\u5fae\u73af\u5883\uff08TME\uff09\u4e2d\u4e0e\u80bf\u7624\u6d88\u9000\u76f8\u5173\u7684TI Tregs\u7684\u51cf\u5c11\u3002\u8fd9\u79cd\u7531CTLA-4\u4ecb\u5bfc\u7684Treg\u8017\u7aed\u4f9d\u8d56\u4e8eTME\u4e2d\u6297CTLA-4\u4e9a\u578b\u548c\u8868\u8fbeFc\u03b3\u53d7\u4f53\uff08Fc\u03b3R\uff09\u7684\u7ec6\u80de\u7684\u5b58\u5728\u3002\u5728\u4eba\u7c7b\u7814\u7a76\u4e2d\uff0c\u89c2\u5bdf\u5230\u4e86\u7c7b\u4f3c\u7684\u73b0\u8c61\uff0c\u4f8b\u5982\uff0cipilimumab\u901a\u8fc7\u81ea\u7136\u6740\u4f24\uff08NK\uff09\u7ec6\u80de\u4ecb\u5bfc\u7684\u6297\u4f53\u4f9d\u8d56\u6027\u7ec6\u80de\u4ecb\u5bfc\u7684\u7ec6\u80de\u6bd2\u6027\uff08ADCC\uff09\u4f5c\u7528\uff0c\u4ece\u5934\u9888\u90e8\u9cde\u72b6\u7ec6\u80de\u764c\u60a3\u8005\u4e2d\u8017\u7aedCTLA-4+ <\/sup>TI Tregs(Fig 29.3a<\/span>)\u3002\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0cipilimumab\u4e5f\u901a\u8fc7\u643a\u5e26Fc\u03b3RIII\u7684\u975e\u7ecf\u5178\u5355\u6838\u7ec6\u80de\u6765\u8bf1\u5bfcADCC\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig 29.3 <\/span>\u9488\u5bf9Tregs\u4e0a\u514d\u75ab\u8c03\u8282\u53d7\u4f53\u7684\u6297\u4f53\u6cbb\u7597\u7b56\u7565\u3002<\/span>(A) \u6297CTLA-4\u5355\u514b\u9686\u6297\u4f53\u80fd\u591f\u8bf1\u5bfc\u4e0e\u80bf\u7624\u6d88\u9000\u76f8\u5173\u7684TI Tregs\u6570\u91cf\u51cf\u5c11\u3002IgG1\u578b\u6297\u4f53ipilimumab\u4e0eCTLA-4\u7ed3\u5408\u540e\uff0c\u53ef\u901a\u8fc7\u6297\u4f53\u4f9d\u8d56\u6027\u7ec6\u80de\u4ecb\u5bfc\u7684\u7ec6\u80de\u6bd2\u6027\uff08ADCC\uff09\u673a\u5236\u4ecb\u5bfcCTLA-4+ <\/sup>Tregs\u7684\u8017\u5c3d\u3002\u76f8\u8f83\u4e4b\u4e0b\uff0cIgG2\u578b\u5355\u514b\u9686\u6297\u4f53\u901a\u8fc7\u963b\u65adCTLA-4\uff0c\u51cf\u5c11\u4e86Treg\u7684\u6291\u5236\u529f\u80fd\uff0c\u5e76\u4fc3\u8fdb\u6548\u5e94T\u7ec6\u80de\u5bf9Treg\u6291\u5236\u7684\u62b5\u6297\u3002<\/span>(B) Tregs\u8868\u9762\u8868\u8fbe\u7684\u5171\u523a\u6fc0\u53d7\u4f53\uff0c\u5982GITR\u548cOX40\uff0c\u53ef\u4ee5\u88ab\u6fc0\u52a8\u578b\u6297\u4f53\u6216\u76f8\u5e94\u7684\u914d\u4f53\u878d\u5408\u86cb\u767d\u7ed3\u5408\u3002\u8fd9\u4e9b\u878d\u5408\u86cb\u767d\u5e26\u6709IgG1 Fc\u90e8\u5206\uff0c\u80fd\u4e0e\u6fc0\u6d3b\u7684Fc\u03b3\u53d7\u4f53\uff08\u5b58\u5728\u4e8eNK\u7ec6\u80de\u3001\u4e2d\u6027\u7c92\u7ec6\u80de\u548c\u5de8\u566c\u7ec6\u80de\u4e0a\uff09\u7ed3\u5408\uff0c\u4ece\u800c\u901a\u8fc7ADCC\u6216\u6297\u4f53\u4f9d\u8d56\u6027\u7ec6\u80de\u541e\u566c\uff08ADCP\uff09\u673a\u5236\u5bfc\u81f4Treg\u7684\u8017\u5c3d\u3002\u6b64\u5916\uff0c\u6297GITR\u6297\u4f53\u8fd8\u53ef\u80fd\u901a\u8fc7\u7834\u574fFoxP3\u7684\u7a33\u5b9a\u6027\uff0c\u5bfc\u81f4Treg\u7684\u529f\u80fd\u7a33\u5b9a\u6027<\/span>\u4e27\u5931\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u96f7\u7c73\u5355\u6297\uff08tremelimumab\uff09\u4f5c\u4e3a\u4e00\u79cdIgG2\u5355\u6297\uff0c\u4e0d\u592a\u53ef\u80fd\u901a\u8fc7ADCC\u673a\u5236\u5bfc\u81f4TI Treg\u7684\u8017\u7aed\u3002\u5728I\u671f\u548cII\u671f\u7814\u7a76\u4e2d\uff0c\u96f7\u7c73\u5355\u6297\u5728\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\u5c55\u793a\u4e86\u4e00\u4e9b\u6709\u6548\u7684\u4e34\u5e8a\u7ed3\u679c\u3002\u7136\u800c\uff0c\u5728\u7b2c\u4e09\u9636\u6bb5\u7684\u7814\u7a76\uff08NCT00257205\uff09\u4e2d\uff0c\u96f7\u7c73\u5355\u6297\u5728\u4f5c\u4e3a\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684\u4e00\u7ebf\u6cbb\u7597\u65b9\u6848\u65f6\uff0c\u4e0e\u4f20\u7edf\u5316\u7597\u76f8\u6bd4\uff0c\u5e76\u672a\u663e\u793a\u51fa\u7edf\u8ba1\u4e0a\u7684\u663e\u8457\u751f\u5b58\u4f18\u52bf\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u53e6\u4e00\u65b9\u9762\uff0cM\u00e9nard\u7b49\u4eba\u7684\u7814\u7a76\u53d1\u73b0\uff0c\u5728\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c\u96f7\u7c73\u5355\u6297\u80fd\u591f\u6062\u590d\u6548\u5e94\u8bb0\u5fc6T\u7ec6\u80de\u7684\u589e\u6b96\uff0c\u8fd9\u8868\u660e\u8be5\u60a3\u8005\u7fa4\u4f53\u5bf9Treg\u7684\u514d\u75ab\u6291\u5236\u529f\u80fd\u4ea7\u751f\u4e86\u4e00\u5b9a\u7684\u62b5\u6297(Fig 29.3a<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u603b\u4e4b\uff0c\u5c3d\u7ba1CTLA-4\u5355\u6297\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u5df2\u663e\u793a\u51fa\u4e00\u5b9a\u7684\u7597\u6548\uff0c\u5bf9\u5b83\u4eec\u5bf9Treg\u7ec6\u80de\u7fa4\u4f53\u7684\u5177\u4f53\u5f71\u54cd\u5c1a\u4e0d\u5145\u5206\u4e86\u89e3\u3002\u66f4\u6df1\u5165\u5730\u63a2\u7d22\u5b83\u4eec\u7684\u4f5c\u7528\u673a\u5236\u5c06\u5bf9\u5f00\u53d1\u66f4\u6709\u6548\u7684\u6cbb\u7597\u65b9\u6cd5\u5927\u6709\u88e8\u76ca\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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<\/p>\n<\/section>\n<\/section>\n

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29.7 \u523a\u6fc0\u6027\u6297\u4f53\u5bf9Treg\u514d\u75ab\u6291\u5236\u6d3b\u6027\u7684\u5f71\u54cd<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u4f5c\u4e3a\u63d0\u9ad8\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u7684\u66ff\u4ee3\u7b56\u7565\u4e4b\u4e00\uff0c\u7814\u7a76\u8005\u4eec\u5df2\u5f00\u59cb\u63a2\u7d22\u9776\u5411\u53c2\u4e0eTreg\u8c03\u8282\u7684\u5171\u523a\u6fc0\u5206\u5b50\u3002\u672c\u8282\u5c06\u91cd\u70b9\u4ecb\u7ecd\u4e24\u4e2a\u4e3b\u8981\u7684\u80bf\u7624\u574f\u6b7b\u56e0\u5b50\uff08TNF\uff09\u53d7\u4f53\u8d85\u5bb6\u65cf\u6210\u5458\uff1aGITR\u548cOX40\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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29.7.1 \u6fc0\u52a8\u6027\u6297GITR\u6297\u4f53<\/p>\n<\/section>\n

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GITR\u662f\u4e00\u79cd\u7ec6\u80de\u8868\u9762\u7684\u5171\u523a\u6fc0\u53d7\u4f53\uff0c\u5b83\u5728Tregs\u4e0a\u9ad8\u5ea6\u8868\u8fbe\uff0c\u5728\u672a\u6210\u719f\u7684\u5e7c\u7a1aT\u7ec6\u80de\u548c\u8bb0\u5fc6T\u7ec6\u80de\u4e0a\u7684\u8868\u8fbe\u8f83\u4f4e\u3002\u7136\u800c\uff0c\u4f20\u7edf\u7684CD4+<\/sup> \u548cCD8+ <\/sup>T\u7ec6\u80de\u5728\u6fc0\u6d3b\u540e\u4f1a\u6682\u65f6\u589e\u5f3aGITR\u7684\u8868\u8fbe\uff0c\u901a\u5e38\u57281-3\u5929\u540e\u8868\u8fbe\u6c34\u5e73\u4e0b\u964d\u3002\u56e0\u6b64\uff0cGITR\u4fe1\u53f7\u7684\u4f5c\u7528\u4f9d\u8d56\u4e8e\u7ec6\u80de\u7c7b\u578b\u548c\u6fc0\u6d3b\u72b6\u6001\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n

\u5728\u901a\u8fc7T\u7ec6\u80de\u53d7\u4f53\uff08TCR\uff09\u523a\u6fc0\u6fc0\u6d3b\u65f6\uff0cGITR\u5bf9Tregs\u548c\u5e38\u89c4CD4+<\/sup>\u3001CD8+ <\/sup>T\u7ec6\u80de\u7684\u5f71\u54cd\u76f8\u53cd\u3002\u901a\u8fc7\u5e94\u7528\u6fc0\u52a8\u6027\u6297GITR\u6297\u4f53\uff08\u5982DTA1\uff09\u3001\u91cd\u7ec4GITR\u914d\u4f53\uff08GITRL\uff09\u6216GITRL\u8f6c\u67d3\u4f53(Fig 29.3B<\/span>)\uff0c\u53ef\u4ee5\u89e3\u9664Treg\u5bf9\u6548\u5e94T\u7ec6\u80de\u7684\u6291\u5236\uff0c\u540c\u65f6\u4fc3\u8fdbCD8+ <\/sup>T\u7ec6\u80de\u7684\u6269\u589e\u548c\u7ec6\u80de\u56e0\u5b50\u7684\u4ea7\u751f\u3002\u8fd9\u79cd\u6548\u5e94\u5728\u4f53\u5916\u5b9e\u9a8c\u53ca\u4f53\u5185\u7684\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u4e2d\u5747\u5f97\u5230\u8bc1\u5b9e\u3002\u5728\u8fd9\u4e9b\u4e34\u5e8a\u524d\u7814\u7a76\u4e2d\uff0c\u523a\u6fc0GITR\u5df2\u88ab\u62a5\u9053\u80fd\u63d0\u9ad8\u6548\u5e94T\u7ec6\u80de\u4e0eTreg\u7684\u6bd4\u4f8b\uff0c\u4ece\u800c\u5728\u8377\u7624\u5c0f\u9f20\u4e2d\u4ea7\u751f\u6709\u5229\u7684\u6297\u80bf\u7624\u6548\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6b64\u5916\uff0cCoe\u7b49\u7814\u7a76\u8005\u5728\u5c0f\u9f20\u6a21\u578b\u4e2d\u53d1\u73b0\uff0c\u7531DTA-1\u4ecb\u5bfc\u7684Treg\u51cf\u5c11\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u6bd4\u5728\u80bf\u7624\u5f15\u6d41\u7684\u6dcb\u5df4\u7ed3\u4e2d\u66f4\u4e3a\u663e\u8457\uff0c\u56e0\u4e3a\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684TI Tregs\u76f8\u8f83\u4e8e\u5faa\u73afTregs\u5177\u6709\u66f4\u9ad8\u7684GITR\u8868\u8fbe\u6c34\u5e73\u3002\u8fd9\u8868\u660eGITR\u53ef\u4f5c\u4e3a\u4e00\u4e2a\u9776\u70b9\uff0c\u7528\u4e8e\u9009\u62e9\u6027\u5730\u8017\u5c3d\u6216\u6291\u5236\u8868\u8fbe\u9ad8\u6c34\u5e73GITR\u7684CD4+<\/sup>FoxP3+ <\/sup>Tregs\uff0c\u540c\u65f6\u4e0d\u5e72\u6270\u5168\u8eab\u7684\u81ea\u6211\u8010\u53d7\u7ef4\u6301\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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GITR\u9776\u5411\u5242\u7684\u4f53\u5185\u6d3b\u6027\u76f8\u5f53\u590d\u6742\uff0c\u5176\u4f5c\u7528\u53ef\u80fd\u4f9d\u8d56\u4e8e\u591a\u79cd\u5df2\u63d0\u51fa\u7684\u673a\u5236(Fig 29.3B<\/span>)\uff0c\u5305\u62ec\uff1a(1)\u901a\u8fc7Fc\u03b3\u53d7\u4f53\u4ecb\u5bfc\u7684Treg\u8017\u5c3d\uff0c(2)\u901a\u8fc7Fas-FasL\u4fe1\u53f7\u6fc0\u6d3b\u8bf1\u5bfc\u7684\u7ec6\u80de\u51cb\u4ea1\uff0c(3)\u6291\u5236Treg\u529f\u80fd\u5e76\u8bf1\u5bfc\u6548\u5e94T\u7ec6\u80de\u5bf9Treg\u6291\u5236\u7684\u62b5\u6297\uff0c\u4ee5\u53ca(4)\u901a\u8fc7\u7834\u574fFoxP3\u7684\u7a33\u5b9a\u6027\u5bfc\u81f4Treg\u7a33\u5b9a\u6027\u4e27\u5931\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6700\u8fd1\uff0c\u533b\u5b66\u514d\u75ab\u9886\u57df\u7684\u516c\u53f8\u5f00\u53d1\u4e86\u4e00\u79cd\u65b0\u578b\u7684\u516d\u805a\u4f53GITRL\uff0c\u540d\u4e3aMEDI1873\uff0c\u5b83\u662f\u57fa\u4e8e\u542b\u6709\u4ebaIgG1 Fc\u7ed3\u6784\u57df\u7684\u878d\u5408\u86cb\u767d\u8bbe\u8ba1\u7684\u3002\u5728\u4f53\u5916\u5b9e\u9a8c\u53caCT26\u80bf\u7624\u6a21\u578b\uff08\u5c0f\u9f20\u7ed3\u76f4\u80a0\u764c\u6a21\u578b\uff09\u4e2d\u7684\u8bc4\u4f30\u8868\u660e\uff0cMEDI1873\u901a\u8fc7\u4e0eFc\u03b3\u53d7\u4f53\u7684\u7ed3\u5408\u589e\u5f3a\u4e86Tregs\u7684\u8017\u5c3d\uff0c\u8fd9\u79cd\u4f5c\u7528\u53ef\u80fd\u662f\u901a\u8fc7Fc\u4ecb\u5bfc\u7684\u6548\u5e94\u529f\u80fd\u5b9e\u73b0\u7684\u3002MEDI1873\u76ee\u524d\u6b63\u5728\u5b9e\u4f53\u7624\u60a3\u8005\u4e2d\u8fdb\u884c\u7b2cI\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff08NCT02583165\uff09\u7684\u8bc4\u4f30\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n
\n

\u6839\u636e\u4e34\u5e8a\u524d\u7684\u7814\u7a76\u7ed3\u679c\uff0c\u5305\u62ec\u4f20\u7edf\u7684GITR\u9776\u5411\u6297\u4f53\u548cGITRL\u86cb\u767d\u878d\u5408\u4f53\u5728\u5185\u7684\u4e00\u4e9b\u836f\u7269\u5df2\u7ecf\u8fdb\u5165\u6216\u5373\u5c06\u8fdb\u5165\u4e34\u5e8a\u8bd5\u9a8c\u9636\u6bb5\uff0c\u9884\u8ba1\u4e0d\u4e45\u5c06\u542f\u52a8\u8fd9\u4e9b\u8bd5\u9a8c\u3002\u8fd9\u4e9b\u7814\u7a76\u6709\u671b\u4e3a\u764c\u75c7\u6cbb\u7597\u63d0\u4f9b\u65b0\u7684\u514d\u75ab\u6cbb\u7597\u7b56\u7565(Table 29.4<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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<\/section>\n<\/section>\n
\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

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Table 29.4<\/span> <\/span>GITR-\u6b63\u5728\u8fdb\u884c\u7684\u8bd5\u9a8c\u4e2d\u7684\u9776\u5411\u836f\u7269<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

29.7.2  OX40\/OX40L\u6fc0\u52a8\u5242<\/p>\n<\/section>\n

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\n

OX40\uff08CD134\uff09\u53ca\u5176\u914d\u4f53OX40L\uff08CD252\uff09\u662f\u80bf\u7624\u574f\u6b7b\u56e0\u5b50\u53d7\u4f53\/\u80bf\u7624\u574f\u6b7b\u56e0\u5b50\uff08TNFR\/TNF\uff09\u8d85\u5bb6\u65cf\u7684\u6210\u5458\uff0c\u5411\u5305\u62ec\u8bb0\u5fc6\u6027CD8+<\/sup>\u6dcb\u5df4\u7ec6\u80de\u3001CD4+<\/sup>\u8f85\u52a9T\u7ec6\u80de\u4e9a\u7fa4\uff08\u5982Th1\u3001Th2\u548cTh17\uff09\u4ee5\u53caCD4+<\/sup> Foxp3+ <\/sup>Tregs\u63d0\u4f9b\u5171\u523a\u6fc0\u4fe1\u53f7\u3002OX40L\u4e3b\u8981\u5728\u6d3b\u5316\u7684\u6297\u539f\u63d0\u5448\u7ec6\u80de\uff08APC\uff09\uff0c\u5c24\u5176\u662f\u6811\u7a81\u72b6\u7ec6\u80de\uff08DC\uff09\u4e0a\u8868\u8fbe\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n

\u6709\u8da3\u7684\u662f\uff0c\u5728\u5c0f\u9f20\u6216\u4eba\u7c7b\u80bf\u7624\u6d3b\u68c0\u7ec4\u7ec7\u4e2d\u5206\u79bb\u7684\u80bf\u7624\u6d78\u6da6\u6027\u6dcb\u5df4\u7ec6\u80de\uff08TIL\uff09\u8868\u8fbe\u7684OX40\u6c34\u5e73\u9ad8\u4e8e\u5916\u5468T\u7ec6\u80de\uff0c\u8fd9\u6709\u52a9\u4e8eT\u7ec6\u80de\u7684\u6fc0\u6d3b\u3001\u589e\u6b96\u548c\u5b58\u6d3b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u76ee\u524d\u5bf9\u4e8eOX40\u5728\u8c03\u8282Treg\u529f\u80fd\u65b9\u9762\u7684\u673a\u5236\u4e86\u89e3\u4ecd\u8f83\u4e3a\u6709\u9650\u3002\u591a\u6570\u5c0f\u9f20\u548c\u4eba\u7c7b\u7684\u7814\u7a76\u663e\u793a\uff0c\u4e0e\u6fc0\u52a8\u5242OX40\u6297\u4f53\u7684\u7ed3\u5408\u53ef\u4ee5\u6539\u53d8Tregs\u7684\u5206\u5316\u548c\u6291\u5236\u6d3b\u6027\uff0c\u540c\u65f6\u4e5f\u53ef\u80fd\u901a\u8fc7\u589e\u5f3a\u6548\u5e94T\u7ec6\u80de\u5bf9Treg\u6291\u5236\u7684\u62b5\u6297\u6765\u95f4\u63a5\u53d1\u6325\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n
\n

\u6700\u8fd1\u7684\u4e00\u9879\u5c0f\u9f20\u7814\u7a76\u62a5\u544a\u79f0\uff0c\u9488\u5bf9OX40\u7684\u6fc0\u52a8\u5242\u6297\u4f53\u80fd\u591f\u9009\u62e9\u6027\u5730\u8017\u5c3d\u8868\u8fbeOX40\u7684TI\u6811\u7a81\u72b6\u7ec6\u80de\u3002\u8fd9\u79cd\u8017\u5c3d\u4f3c\u4e4e\u662f\u901a\u8fc7\u6297\u4f53\u4f9d\u8d56\u6027\u7ec6\u80de\u4ecb\u5bfc\u7684\u7ec6\u80de\u6bd2\u6027\uff08ADCC\uff09\u5b9e\u73b0\u7684\uff0c\u4f9d\u8d56\u4e8e\u9ad3\u7cfb\u7ec6\u80de\u548c\u81ea\u7136\u6740\u4f24\uff08NK\uff09\u7ec6\u80de\u8868\u8fbe\u7684Fc\u03b3\u53d7\u4f53\u7684\u6fc0\u6d3b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u7efc\u4e0a\u6240\u8ff0\uff0c\u9488\u5bf9OX40\/OX40L\u8f74\u7684\u9776\u5411\u6cbb\u7597\u4e3a\u6297\u764c\u514d\u75ab\u6cbb\u7597\u63d0\u4f9b\u4e86\u4e00\u79cd\u6709\u524d\u666f\u7684\u7b56\u7565\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u591a\u4e2a\u4e34\u5e8a\u524d\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u4e2d\uff0c\u5305\u62ec\u6297OX40\u5355\u6297\u548cOX40L-Fc\u878d\u5408\u86cb\u767d(Fig 29.3B<\/span>)\u5728\u5185\u7684OX40\/OX40L\u9776\u5411\u5236\u5242\u4f5c\u4e3a\u5355\u72ec\u7597\u6cd5\u5e94\u7528\u65f6\uff0c\u5df2\u7ecf\u663e\u793a\u51fa\u5728\u589e\u5f3a\u4fdd\u62a4\u6027\u6297\u80bf\u7624\u514d\u75ab\u548c\u6539\u5584\u65e0\u7624\u751f\u5b58\u7387\u65b9\u9762\u5177\u6709\u5e0c\u671b\u7684\u7ed3\u679c\u3002<\/p>\n

\u6b64\u5916\uff0c\u591a\u9879\u5c0f\u9f20\u7814\u7a76\u8868\u660e\uff0c\u5f53\u6297OX40\u836f\u7269\u4e0e\u5176\u4ed6\u514d\u75ab\u8c03\u8282\u6297\u4f53\uff08\u4f8b\u5982\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\uff09\u6216\u6cbb\u7597\u6027\u764c\u75c7\u75ab\u82d7\u8054\u5408\u4f7f\u7528\u65f6\uff0c\u53ef\u4ee5\u8fdb\u4e00\u6b65\u63d0\u5347\u6297\u80bf\u7624\u6548\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
<\/section>\n<\/section>\n
\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

Table 29.5<\/span> <\/span>OX40-\u6b63\u5728\u8fdb\u884c\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u7684\u8c03\u8282\u5242<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u76ee\u524d\uff0c\u81f3\u5c11\u6709\u516d\u79cd\u6297OX40\u6fc0\u52a8\u5242\u5355\u6297\u548c\u4e00\u79cdOX40L-Fc\u878d\u5408\u86cb\u767d\u6b63\u5728\u7531\u591a\u5bb6\u516c\u53f8\u5f00\u53d1\uff0c\u5e76\u6b63\u5728\u8fdb\u884c\u65e9\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u4ee5\u8bc4\u4f30\u5176\u5728\u6cbb\u7597\u665a\u671f\u5b9e\u4f53\u6076\u6027\u80bf\u7624\u4e2d\u7684\u6f5c\u5728\u6548\u679c\u3002\u8fd9\u4e9b\u8bd5\u9a8c\u7684\u8fdb\u5c55\u5c06\u4e3a\u672a\u6765\u7684\u764c\u75c7\u6cbb\u7597\u63d0\u4f9b\u91cd\u8981\u7684\u4e34\u5e8a\u6570\u636e(Table 29.5<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

9B12\u662f\u4e00\u79cd\u6fc0\u52a8\u6027\u5c0f\u9f20\u6297\u4ebaOX40\u5355\u6297\uff0c\u4e5f\u662f2003\u5e74\u9996\u6b21\u8fdb\u5165\u4e34\u5e8a\u7684\u6297\u4f53\u4e4b\u4e00\u3002\u8be5\u6297\u4f53\u5df2\u5728\u5e38\u89c4\u6cbb\u7597\u65e0\u6548\u7684\u665a\u671f\u5b9e\u4f53\u764c\uff08\u5305\u62ec\u9ed1\u8272\u7d20\u7624\u3001\u80be\u764c\u3001\u5c3f\u9053\u764c\u3001\u524d\u5217\u817a\u764c\u548c\u80c6\u7ba1\u764c\uff09\u60a3\u8005\u4e2d\u8fdb\u884c\u4e86I\u671f\u8bd5\u9a8c\uff08NCT01644968\uff09\u3002\u6297OX40\u5355\u6297\u7684\u8010\u53d7\u6027\u826f\u597d\uff0cCurti\u62a5\u9053\u79f0\uff0c\u572830\u540d\u60a3\u8005\u4e2d\uff0c\u670912\u540d\u60a3\u8005\u5728\u4ec5\u4e00\u4e2a\u6cbb\u7597\u5468\u671f\u540e\u81f3\u5c11\u6709\u4e00\u4e2a\u8f6c\u79fb\u75c5\u7076\u51fa\u73b0\u6d88\u9000\u3002\u6b64\u5916\uff0c\u7814\u7a76\u8fd8\u53d1\u73b0\u80bf\u7624\u5185\uff08TI\uff09Tregs\u8868\u8fbe\u7684OX40\u6bd4\u4f8b\u9ad8\u8fbe50%\uff0c\u8fd9\u652f\u6301\u4e86\u5c0f\u9f20\u7814\u7a76\u4e2d\u89c2\u5bdf\u5230\u7684\u6297OX40\u6297\u4f53\u53ef\u80fd\u8c03\u8282\u80bf\u7624\u4e2dTreg\u529f\u80fd\u7684\u5047\u8bbe\u3002\u7136\u800c\uff0c\u7814\u7a76\u4e2d\u5e76\u672a\u62a5\u544a\u80bf\u7624\u5185Tregs\u6570\u91cf\u7684\u51cf\u5c11\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u76ee\u524d\uff0c\u5305\u62ecMEDI6469\uff08\u9f20\u6297\u4ebaOX40 mAb\uff09\uff0cMEDI0562\uff08\u901a\u8fc7\u4eba\u6e90\u5316MEDI6469\u5f00\u53d1\u7684\uff09\uff0cMOXR0916\u548cGSK3174998\uff08\u4e24\u79cd\u4eba\u6e90\u5316IgG1\u578b\u6fc0\u52a8\u6027\u6297OX40 mAb\uff09\uff0cPF-04518600\uff08\u5168\u4eba\u514d\u75ab\u7403\u86cb\u767dG2\u6fc0\u52a8\u6027\u6297OX40 mAb\uff09\u4ee5\u53caINCAGN01949\uff08\u5168\u4ebaIgG1\u6fc0\u52a8\u6027\u6297OX40 mAb\uff09\u5728\u5185\u7684\u51e0\u79cd\u6297OX40\u5355\u6297\u6b63\u5904\u4e8e\u4e0d\u540c\u9636\u6bb5\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e2d(Table 29.5<\/span>)\u3002\u8fd9\u4e9b\u6297\u4f53\u6b63\u5728\u9488\u5bf9\u5305\u62ec\u665a\u671f\u6216\u8f6c\u79fb\u6027\u524d\u5217\u817a\u764c\u3001\u4e73\u817a\u764c\u3001\u7ed3\u76f4\u80a0\u764c\u3001\u5934\u9888\u90e8\u9cde\u72b6\u7ec6\u80de\u764c\uff08HNSCC\uff09\u548c\u4fb5\u88ad\u6027B\u7ec6\u80de\u6dcb\u5df4\u7624\u7b49\u591a\u79cd\u764c\u75c7\u7c7b\u578b\u8fdb\u884c\u6d4b\u8bd5\u3002\u8fd9\u4e9b\u4e0d\u540c\u7684\u6297OX40\u5355\u6297\u6b63\u4f5c\u4e3a\u5355\u4e00\u7597\u6cd5\u6216\u4e0e\u5176\u4ed6\u7597\u6cd5\u8054\u5408\u4f7f\u7528\u8fdb\u884c\u8bc4\u4f30\uff0c\u5305\u62ec\u4e0e\u653e\u5c04\u6cbb\u7597\u3001\u73af\u78f7\u9170\u80fa\u3001\u5229\u59a5\u6614\u5355\u6297\uff08\u6297CD20\uff09\u3001MEDI4736\/\u963f\u66ff\u5511\u5355\u6297\/\u5ea6\u4f10\u5355\u6297\uff08\u6297PD-L1\uff09\u3001\u57f9\u5e03\u7f57\u5229\u5355\u6297\uff08\u6297PD-1\uff09\u3001\u7279\u96f7\u7c73\u5355\u6297\uff08\u6297CTLA-4\uff09\u3001PF-05082566\uff084-1BB\u6fc0\u52a8\u5242\uff09\u548c\u8d1d\u4f10\u5355\u6297\uff08\u6297\u8840\u7ba1\u5185\u76ae\u751f\u957f\u56e0\u5b50\uff09\u7b49\u7684\u8054\u5408\u6cbb\u7597(Table 29.5<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u6700\u8fd1\uff0c\u57282014\u5e74\uff0cMedImmune LLC\u5f00\u53d1\u7684\u4e00\u79cd\u4ebaOX40\u914d\u4f53\u878d\u5408\u86cb\u767dMEDI6383\u4e5f\u6b63\u5728\u5bf9\u590d\u53d1\u6216\u8f6c\u79fb\u7684\u5b9e\u4f53\u80bf\u7624\u8fdb\u884c\u6d4b\u8bd5\uff0c\u65e2\u53ef\u5355\u72ec\u4f7f\u7528\uff0c\u4e5f\u53ef\u4e0e\u5ea6\u4f10\u5355\u6297\uff08\u6297PD-L1\uff09\u8054\u5408\u4f7f\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

29.8 CD39-CD73-A2aR\u901a\u8def\u963b\u65ad\uff1a\u9488\u5bf9Treg\u7684\u9776\u5411\u6cbb\u7597\u7b56\u7565<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u7ec4\u7ec7\u635f\u4f24\u6216\u7ec6\u80de\u5e94\u6fc0\u72b6\u6001\u4e0b\uff0cATP\u53ca\u5176\u4ee3\u8c22\u4ea7\u7269\uff08ADP\u3001AMP\u548c\u817a\u82f7\uff09\u4f1a\u88ab\u91ca\u653e\u5230\u7ec6\u80de\u5916\u95f4\u9699\u4e2d\uff0c\u8fd9\u4e9b\u5206\u5b50\u5728\u7ef4\u6301\u514d\u75ab\u7a33\u6001\u4e2d\u8d77\u7740\u5173\u952e\u4f5c\u7528\u3002\u7136\u800c\uff0c\u80bf\u7624\u7ec6\u80de\u53ef\u4ee5\u64cd\u7eb5\u8fd9\u4e9b\u5206\u5b50\uff0c\u901a\u8fc7\u751f\u7406\u53cd\u9988\u673a\u5236\u7684\u8d1f\u8c03\u63a7\u6765\u9003\u907f\u514d\u75ab\u76d1\u89c6\uff0c\u4ece\u800c\u6291\u5236\u6297\u80bf\u7624T\u7ec6\u80de\u53cd\u5e94\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u80de\u5916\u6838\u82f7\u9178\u9176CD39\u548cCD73\u5206\u522b\u5c06\u7ec6\u80de\u5916\u7684ATP\u5206\u89e3\u4e3aAMP\uff0c\u53caAMP\u8fdb\u4e00\u6b65\u5206\u89e3\u4e3a\u817a\u82f7\uff0c\u8fd9\u4e24\u79cd\u9176\u5728\u5c0f\u9f20\u548c\u4eba\u7c7b\u7684Tregs\u4e0a\u9ad8\u8868\u8fbe(Fig 29.4<\/span>)\u3002\u6b64\u5916\uff0c\u5305\u62ecTregs\u5728\u5185\u7684T\u6dcb\u5df4\u7ec6\u80de\u4e0a\u4e3b\u8981\u8868\u8fbe\u9ad8\u4eb2\u548c\u529b\u7684\u817a\u82f72a\u53d7\u4f53\uff08A2aR\uff09\u548c\u4f4e\u4eb2\u548c\u529b\u7684\u817a\u82f72b\u53d7\u4f53\uff08A2bR\uff09\u3002A2a\u548cA2b\u53d7\u4f53\u7684\u6fc0\u6d3b\u4f1a\u5bfc\u81f4\u663e\u8457\u7684\u514d\u75ab\u6291\u5236\u6548\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
<\/section>\n<\/section>\n
\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

Fig 29.4 <\/span>CD39-CD73-A2aR\u901a\u8def\u963b\u65ad\uff1a\u9488\u5bf9Tregs\u7684\u9776\u5411\u6cbb\u7597\u7b56\u7565\u3002\u80bf\u7624\u7ec6\u80de\u901a\u8fc7\u514d\u75ab\u539f\u6027\u6b7b\u4ea1\u5c06ATP\u53ca\u5176\u4ee3\u8c22\u4ea7\u7269\uff08ADP\u3001AMP\u548c\u817a\u82f7\uff09\u91ca\u653e\u5230\u80bf\u7624\u5fae\u73af\u5883\uff08TME\uff09\u4e2d\u3002\u4f5c\u4e3a\u7f3a\u6c27\u53cd\u5e94\u7684\u4e00\u90e8\u5206\uff0c\u5c06ATP\u8f6c\u5316\u4e3a\u817a\u82f7\u7684\u80de\u5916\u6838\u82f7\u9178\u9176\uff08ECN\uff0c\u5305\u62ecCD73\u548cCD39\uff09\u4ee5\u53ca\u817a\u82f7\u53d7\u4f53\u5728\u80bf\u7624\u548c\u514d\u75ab\u7ec6\u80de\u4e0a\u8fc7\u5ea6\u8868\u8fbe\u3002\u817a\u82f7\u4e0e\u5176\u53d7\u4f53\u7ed3\u5408\uff0c\u4ecb\u5bfc\u4e86\u591a\u79cd\u514d\u75ab\u53cd\u5e94\u7684\u6291\u5236\uff0c\u5305\u62ecTh1\u3001CD4+<\/sup>\u548c\u7ec6\u80de\u6bd2\u6027T\u6dcb\u5df4\u7ec6\u80de\uff08CTL\uff09\u7684\u6d3b\u52a8\u6291\u5236\uff0c\u4ee5\u53ca\u4fc3\u8fdb\u514d\u75ab\u6291\u5236\u7ec6\u80de\uff08\u5982Tregs\u548c\u7c92\u7ec6\u80de\u578b\u9ad3\u7cfb\u6291\u5236\u7ec6\u80deMDSCs\uff09\u7684\u589e\u6b96\u548c\u6811\u7a81\u72b6\u7ec6\u80de\u53caM2\u578b\u5de8\u566c\u7ec6\u80de\u7684\u8010\u53d7\u6027\u8bf1\u5bfc\u3002\u817a\u82f7\u5728\u4fc3\u8fdb\u80bf\u7624\u7ec6\u80de\u7684\u751f\u957f\u548c\u5b58\u6d3b\u4e2d\u4e5f\u626e\u6f14\u7740\u5173\u952e\u89d2\u8272\u3002\u76ee\u524d\uff0c\u9488\u5bf9\u817a\u82f7-CD73-CD39\u9014\u5f84\u7684A2aR\u62ee\u6297\u5242\u548c\u5355\u514b\u9686\u6297\u4f53\u6b63\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u8fdb\u884c\u6d4b\u8bd5\uff0c\u4ee5\u514b\u670d\u817a\u82f7\u4ecb\u5bfc\u7684\u514d\u75ab\u6291\u5236\uff0c\u589e\u5f3a\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

A2aR\u5728Tregs\u4e0a\u7684\u6d3b\u5316\u4e0d\u4ec5\u589e\u5f3a\u4e86\u5b83\u4eec\u7684CTLA-4\u548cPD-1\u8868\u8fbe\uff08\u5728\u4f53\u5916\u7814\u7a76\u4e2d\u89c2\u5bdf\u5230\uff09\uff0c\u8fd8\u4fc3\u8fdb\u4e86\u5b83\u4eec\u4ece\u5e7c\u7a1aT\u7ec6\u80de\u5230\u5177\u6709\u9ad8\u514d\u75ab\u6291\u5236\u6d3b\u6027\u7684Tregs\u7684\u5206\u5316\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u591a\u79cd\u764c\u75c7\u4e2d\uff0c\u7531\u4e8e\u7f3a\u6c27\u8bf1\u5bfc\u7684\u80de\u5916\u6838\u82f7\u9178\u9176CD73\u548cCD39\u7684\u8fc7\u5ea6\u8868\u8fbe\uff0c\u817a\u82f7\u5728\u80bf\u7624\u90e8\u4f4d\u7684\u5927\u91cf\u91ca\u653e\u8fdb\u4e00\u6b65\u52a0\u5267\u4e86\u5176\u4fc3\u80bf\u7624\u4f5c\u7528(Fig 29.4<\/span>)\u3002\u817a\u82f7\u7684\u8fd9\u4e00\u4f5c\u7528\u901a\u8fc7\u4ee5\u4e0b\u673a\u5236\u5b9e\u73b0\uff1a(1)\u901a\u8fc7A2aR\u6291\u5236\u6297\u80bf\u7624\u7684Th1 CD4+<\/sup>\u548c\u7ec6\u80de\u6bd2\u6027CD8+ <\/sup>T\u7ec6\u80de\uff0c(2)\u4fc3\u8fdb\u514d\u75ab\u6291\u5236\u7ec6\u80de\uff08\u5982Tregs\u548c\u7c92\u7ec6\u80de\u578b\u9ad3\u7cfb\u6291\u5236\u7ec6\u80deMDSCs\uff09\u7684\u589e\u6b96\uff0c\u4ee5\u53ca(3)\u8bf1\u5bfc\u6811\u7a81\u72b6\u7ec6\u80de\u548c2\u578b\u5de8\u566c\u7ec6\u80de\u7684\u8010\u53d7\u6027(Fig 29.4<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u764c\u75c7\u5fae\u73af\u5883\u4e2d\u7684\u8fd9\u4e9b\u53d1\u73b0\u4fc3\u4f7f\u7814\u7a76\u4eba\u5458\u5728\u5c0f\u9f20\u6a21\u578b\u548c\u4eba\u7c7b\u60a3\u8005\u4e2d\u63a2\u7d22\u9776\u5411CD73-CD39\u9014\u5f84\u4ee5\u514b\u670d\u817a\u82f7\u4ecb\u5bfc\u7684\u514d\u75ab\u6291\u5236\u7684\u6f5c\u529b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u9274\u4e8e\u5168\u8eab\u6027\u9776\u5411Treg\u53ef\u80fd\u4e25\u91cd\u5f71\u54cd\u5916\u5468\u514d\u75ab\u7a33\u6001\uff0c\u5f00\u53d1\u66f4\u5177\u9009\u62e9\u6027\u7684\u65b9\u6cd5\u6765\u9650\u5236\u80bf\u7624\u5185Treg\u7684\u514d\u75ab\u6291\u5236\u4f5c\u7528\u663e\u5f97\u5c24\u4e3a\u91cd\u8981\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u672c\u6587\u7531Oncolab\u5fae\u4fe1\u516c\u4f17\u53f7\u7ffb\u8bd1\u6574\u7406\u81eaOncoimmunology: A Practical Guide for Cancer Immunotherapy\uff0c\u4ec5\u7528\u4e8e\u5b66\u4e60\u4ea4\u6d41\u4f7f\u7528\uff0c\u5982\u9700\u8d2d\u4e70\u539f\u7248\u4e66\u7c4d\u53ef\u70b9\u51fb\u9605\u8bfb\u539f\u6587\u8d2d\u4e70\u3002<\/span>
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\u2014 THE  END \u2014<\/span><\/p>\n


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\u6765\u6e90 | Oncoimmunology: A Practical Guide <\/span><\/p>\n

for Cancer Immunotherapy<\/span><\/p>\n

\u521d\u7a3f\u7ffb\u8bd1 | \u7f57\u4f73\u4f73<\/span><\/p>\n

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\u70b9\u4eae\u8d5e\u4e0e\u5728\u770b <\/span><\/p>\n

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\u672c\u7bc7\u6587\u7ae0\u6765\u6e90\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7: OncoLab <\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

\u4e0a\u671f\u5185\u5bb9\uff1a\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c29\u7ae0 \u51cf\u5c11\u80bf\u7624\u5185\u8c03\u8282\u6027T\u7ec6\u80de\u7684\u7b56\u7565\uff08\u4e0a\uff09 29.5 \u9488\u5bf9Treg\u7684\u6297\u8840\u7ba1\u751f\u6210\u7597\u6cd5 \u8840…<\/p>\n","protected":false},"author":1,"featured_media":3590,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[65],"tags":[],"_links":{"self":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/posts\/3595"}],"collection":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/comments?post=3595"}],"version-history":[{"count":0,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/posts\/3595\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/media\/3590"}],"wp:attachment":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/media?parent=3595"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/categories?post=3595"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/tags?post=3595"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}