{"id":33108,"date":"2018-11-01T00:00:00","date_gmt":"2018-10-31T16:00:00","guid":{"rendered":"https:\/\/case.ntu.edu.tw\/blog\/?p=33108"},"modified":"2018-10-26T10:41:51","modified_gmt":"2018-10-26T02:41:51","slug":"%e5%85%8d%e7%96%ab%e6%aa%a2%e6%9f%a5%e9%bb%9e%e6%8a%91%e5%88%b6%e5%8a%91%e7%9a%84%e6%ad%a1%e5%96%9c%e8%88%87%e6%82%b2%e5%82%b7-%ef%bc%881%ef%bc%89","status":"publish","type":"post","link":"https:\/\/case.ntu.edu.tw\/blog\/?p=33108","title":{"rendered":"\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7684\u6b61\u559c\u8207\u60b2\u50b7 (\u4e0a)"},"content":{"rendered":"

\u64b0\u6587\uff5c\u99f1\u5b9b\u7433<\/strong><\/p>\n

\u6700\u8fd1\u5e7e\u5e74\uff0c\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\uff08immune checkpoint blockade\uff09\u5c0d\u6bb2\u6ec5\u764c\u75c7\u7684\u9b54\u529b\uff0c\u50cf\u662f\u6297\u764c\u91ab\u7642\u9818\u57df\u7684\u54c8\u5229\u6ce2\u7279\uff1a\u4e0d\u8ad6\u662f\u7576\u524d\u7684\u6210\u679c\u3001\u9084\u662f\u672a\u4f86\u7684\u6f5b\u529b\uff0c\u90fd\u53d7\u5230\u773e\u6240\u77da\u76ee\u3002\u800c\u52aa\u529b\u63a8\u52d5\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u65bc\u6297\u764c\u91ab\u7642\u7684\u5169\u4f4d\u79d1\u5b78\u5bb6\uff1aJames Alison \u535a\u58eb\u8207\u672c\u5eb6\u4f51\u535a\u58eb\uff0c\u4e5f\u7372\u5f97\u4e86\u4eca\u5e74\u5ea6\u7684\u8afe\u8c9d\u723e\u91ab\u5b78\u734e\u6b8a\u69ae\u3002\u5230\u5e95\u70ba\u4ec0\u9ebc\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7528\u65bc\u6297\u764c\u91ab\u7642\u6642\uff0c\u80fd\u6709\u5982\u6b64\u5353\u6548\uff1f\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7684\u6297\u764c\u8def\uff0c\u53c8\u6709\u4ec0\u9ebc\u56f0\u5883\u9700\u8981\u79d1\u5b78\u5bb6\u5011\u518d\u52a0\u628a\u52c1\uff0c\u52aa\u529b\u60f3\u51fa\u5c0d\u7b56\u5462\uff1f<\/p>\n

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\u514d\u75ab\u6aa2\u67e5\u9ede\uff0c\u4e5f\u50cf\u8eab\u9ad8\u9650\u5236\u6aa2\u67e5\u9ede\u4e00\u6a23\uff0c\u53ef\u4ee5\u964d\u4f4e\u5c0f\u5b69\u610f\u5916\u51fa\u4e8b\u7684\u6a5f\u7387\u3002T \u7d30\u80de\u5728\u555f\u52d5\u514d\u75ab\u53cd\u61c9\u4e4b\u524d\uff0c\u5fc5\u9808\u8981\u901a\u904e\u514d\u75ab\u6aa2\u67e5\u9ede\u7684\u76e4\u67e5\uff0c\u907f\u514d T \u7d30\u80de\u5728\u4e0d\u8a72\u6d3b\u5316\u7684\u6642\u5019\u537b\u904e\u5ea6\u53cd\u61c9\u4e86\uff0c\u653b\u64ca\u4e86\u7121\u8f9c\u7684\u81ea\u8eab\u7d30\u80de\uff0c\u800c\u5f15\u767c\u81ea\u9ad4\u514d\u75ab\u75be\u75c5\u3002<\/p>\n

\"\"<\/a><\/p>\n

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\u76ee\u524d\uff0c\u7528\u65bc\u6297\u764c\u7684\u514d\u75ab\u6aa2\u67e5\u9ede\u4e3b\u8981\u5c31\u5169\u5927\u985e\uff1a\u5176\u4e00\uff0c\u662f CTLA-4 \u9019\u500b\u6aa2\u67e5\u9ede\uff1b\u5176\u4e8c\uff0c\u662f PD-1 \u6aa2\u67e5\u9ede\u3002\u9019\u5169\u5927\u985e\u6aa2\u67e5\u9ede\u7684\u4f5c\u7528\u6a5f\u8f49\u4e0d\u4e00\u6a23\uff0c\u56e0\u6b64\uff0c\u81e8\u5e8a\u4e0a\u4e5f\u5728\u7a4d\u6975\u63a2\u8a0e\u5c07\u9019\u5169\u500b\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u5408\u4f75\u4f7f\u7528\u7684\u53ef\u80fd\u6027\u8207\u7642\u6548\uff0c\u770b\u770b\u96d9\u7ba1\u9f4a\u4e0b\u662f\u4e0d\u662f\u53ef\u4ee5\u9054\u5230\u4e00\u52a0\u4e00\u5927\u65bc\u4e8c\u7684\u597d\u8655\u3002<\/p>\n

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CTLA-4 \u9019\u500b\u514d\u75ab\u6aa2\u67e5\u9ede\u4e3b\u8981\u662f\u5728 T \u7d30\u80de\u6d3b\u5316\u7684\u521d\u671f\uff0c\u4e5f\u5c31\u662f T \u7d30\u80de\u8ddf\u6297\u539f\u5448\u73fe\u7d30\u80de\u4e92\u52d5\u9019\u6bb5\u6642\u9593\u88e1\u3002T \u7d30\u80de\u8981\u80fd\u5920\u88ab\u6d3b\u5316\uff0c\u9700\u8981\u6709\u4f86\u81ea T \u7d30\u80de\u53d7\u9ad4\uff08T cell receptor\uff09\u8207 CD28\uff08\u5e38\u53eb\u505a costimulation\uff09\u7684\u96d9\u91cd\u8a8d\u8b49\u3002\u7121\u7368\u6709\u5076\u5730\uff0cCTLA-4 \u8ddf CD28 \u5c0d\u7d50\u5408\u53d7\u9ad4\u7684\u54c1\u5473\u662f\u4e00\u6a21\u4e00\u6a23\uff0c\u4f46\u5169\u500b\u86cb\u767d\u7684\u529f\u80fd\u537b\u5357\u8f45\u5317\u8f4d\u3002CD28 \u80fd\u4fc3\u9032 T \u7d30\u80de\u6d3b\u5316\uff0cCTLA-4 \u537b\u662f\u626e\u6f14\u8457\u6291\u5236\u7684\u89d2\u8272\uff0c\u8ddf CD28 \u5531\u53cd\u8abf\u3002CTLA-4 \u672c\u4f86\u5728\u7d30\u80de\u8cea\u5167\uff0c\u7576 T \u7d30\u80de\u53d7\u9ad4\u627e\u5230\u3001\u4e26\u7d50\u5408\u4e0a\u5176\u5c08\u4e00\u6027\u7684\u6297\u539f\u4e4b\u5f8c\uff0cCTLA-4 \u6703\u4e00\u8e8d\u4e0a\u7d30\u80de\u8868\u9762\u3002\u800c\u56e0\u7232 CTLA-4 \u5c0d\u53d7\u9ad4\u7684\u7d50\u5408\u89aa\u5408\u529b\u8981\u6bd4 CD28 \u5927\u4e0a\u8a31\u591a\uff0c\u56e0\u6b64\u6703\u963b\u6493 CD28 \u548c\u53d7\u9ad4\u7d50\u5408\u3002\u6545\u800c\uff0cCTLA-4 \u514d\u75ab\u6aa2\u67e5\u9ede\u80fd\u5920\u963b\u7919\u6297\u539f\u5448\u73fe\u7d30\u80de\u6d3b\u5316\u5177\u6709\u6297\u764c\u5c08\u4e00\u6027\u7684 T \u7d30\u80de\u3002\u56e0\u6b64\uff0c\u5982\u679c\u85c9\u7531 anti-CTLA-4 \u7684\u6297\u9ad4\u4f86\u963b\u65b7 CTLA-4 \u7684\u6291\u5236\u6027\u8a0a\u606f\uff0c\u5c31\u53ef\u4ee5\u9632\u6b62 CTLA-4 \u4f86\u58de\u4e8b\u3002\u53ea\u8981\u6c92\u6709 CTLA-4 \u5f9e\u4e2d\u5531\u53cd\u8abf\uff0c\u5177\u6709\u6297\u764c\u80fd\u529b\u7684 T \u7d30\u80de\uff0c\u5c31\u80fd\u5920\u7121\u7919\u5730\u6536\u5230\u6297\u539f\u5448\u73fe\u7d30\u80de\u7684\u5c0f\u9053\u6d88\u606f\uff0c\u800c\u8d95\u7dca\u555f\u7a0b\u6bba\u6575\u53bb\u3002<\/p>\n

\u81f3\u65bc PD-1 \u514d\u75ab\u6aa2\u67e5\u9ede\u5247\u662f\u767c\u751f\u5728\u816b\u7624\u7d44\u7e54\u88e1\u3002\u63a5\u5230\u901a\u98a8\u5831\u4fe1\u5f8c\u7684 T \u7d30\u80de\u555f\u7a0b\u6bba\u6575\uff0c\u53bb\u5c0b\u627e\u8ddf\u6297\u539f\u5448\u73fe\u7d30\u80de\u6240\u5831\u4fe1\u7684\u8b8a\u7570\u6297\u539f\u5230\u5e95\u8eab\u5728\u4f55\u8655\u3002\u6d3b\u5316\u7684 T \u7d30\u80de\u5f80\u5f80\u6703\u555f\u52d5 PD-1 \u7684\u8868\u73fe\uff0c\u800c\u6709\u4e86\u9019\u7b2c\u4e8c\u500b\u514d\u75ab\u6aa2\u67e5\u9ede\uff0c\u4e5f\u662f\u5177\u6709\u514d\u75ab\u6291\u5236\u6027\u3002PD-1 \u7684\u7d50\u5408\u53d7\u9ad4\u6709\u5169\u500b\uff0c\u4e00\u500b\u662f PD-L1\uff0c\u53e6\u4e00\u500b\u662f PD-L2\u3002\u7576 T \u7d30\u80de\u555f\u52d5\u514d\u75ab\u53cd\u61c9\u6642\uff0c\u5e38\u6703\u5206\u6ccc\u5e72\u64fe\u7d20\uff08IFN- g\uff09\u3002\u8a31\u591a\u9ad4\u7d30\u80de\u5728\u63a5\u6536\u5230\u5e72\u64fe\u7d20\u7684\u8a0a\u606f\u6642\uff0c\u90fd\u6703\u8868\u73fe PD-L1\uff1b\u9019\u4e5f\u5305\u62ec\u4e86\u764c\u7d30\u80de\u3002<\/p>\n

\u56e0\u6b64\uff0c\u5728\u764c\u7d30\u80de\u7fa4\u805a\u7684\u8b8a\u7570\u816b\u7624\u7d44\u7e54\u88e1\uff0c\u5e38\u5e38\u53ef\u4ee5\u770b\u5230\u5927\u91cf\u7684 PD-L1 \u8868\u73fe\uff0c\u9019\u50cf\u662f\u4e82\u5beb\u8eab\u9ad8\u9650\u5236\u7684\u300c\u5047\u4f48\u544a\u300d\u4e00\u6a23\u3002T \u7d30\u80de\u5c31\u7b97\u55c5\u51fa\u4e86\u8b8a\u7570\u7d44\u7e54\u7684\u4e0d\u5c0d\u52c1\uff0c\u4e56\u4e56\u770b\u4f48\u544a\u7684 T \u7d30\u80de\u4e5f\u5c31\u4e56\u4e56\u7684\u4e0d\u4e82\u52d5\uff0c\u5978\u8a08\u5f97\u901e\u7684\u764c\u7d30\u80de\u81ea\u7136\u4e5f\u5c31\u5f97\u4ee5\u9b06\u4e00\u53e3\u6c23\u3002<\/p>\n

\u4f46\u662f\uff0c\u85c9\u7531\u7d66\u4e88\u764c\u75c7\u75c5\u60a3 anti-PD-1 \u6297\u9ad4\uff0c\u6216\u662f anti-PD-1L \u6297\u9ad4\uff0c\u5c31\u53ef\u4ee5\u501f\u6a5f\u963b\u6493 T \u7d30\u80de\u4e0a\u7684 PD-1 \u548c\u764c\u7d30\u80de\u8eab\u4e0a\u7684 PD-L1 \u7d50\u5408\u3002\u5982\u6b64\uff0c\u5c31\u50cf\u662f\u628a\u764c\u75c7\u7d44\u7e54\u88e1\u7684\u6240\u6709\u8eab\u9ad8\u9650\u5236\u4f48\u544a\u901a\u901a\u6495\u6389\u4e00\u6a23\uff0cT \u7d30\u80de\u4e5f\u5c31\u50cf\u662f\u9032\u5230\u901a\u884c\u7121\u963b\u7684\u904a\u6a02\u5712\uff0c\u53ef\u4ee5\u73a9\u904d\u904a\u6a02\u8a2d\u65bd\u4e00\u822c\u7684\u5c07\u764c\u7d30\u80de\u6bba\u6ec5\u3002<\/p>\n

\u4f46\u5947\u602a\u7684\u662f\uff0c\u96d6\u7136\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u7642\u6cd5\u5c0d\u65bc\u5c0d\u6297\u764c\u75c7\u8d85\u7d1a\u6709\u6548\uff0c\u537b\u4f3c\u4e4e\u53ea\u5c0d\u4e00\u90e8\u5206\u7684\u75c5\u4eba\u6709\u6548\u3002\u9019\u662f\u70ba\u4ec0\u9ebc\u5462\uff1f\u8b93\u6211\u5011\u5728\u4e0b\u4e00\u7bc7\u518d\u4f86\u63ed\u66c9\u5427\uff01<\/p>\n

 <\/p>\n

\u53c3\u8003\u8cc7\u6599\uff1a<\/strong><\/p>\n

    \n
  1. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018 Mar 23;359(6382):1350-1355. doi: 10.1126\/science.aar4060. Epub 2018 Mar 22. Review. PMID: 29567705<\/li>\n
  2. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015 Apr 13;27(4):450-61. doi: 10.1016\/j.ccell.2015.03.001. Epub 2015 Apr 6.<\/li>\n
  3. Philippe Immune checkpoint blockade in hematologic malignancies. Blood 2015 125:3393-3400; doi: https:\/\/doi.org\/10.1182\/blood-2015-02-567453<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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