{"id":2799,"date":"2023-01-15T21:20:02","date_gmt":"2023-01-15T13:20:02","guid":{"rendered":"http:\/\/oncolab.cn\/index.php\/2023\/01\/15\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac16%e7%ab%a0-%e5%9f%ba%e4%ba%8enk%e7%bb%86%e8%83%9e%e7%9a%84%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e6%b2%bb%e7%96%97%ef%bc%88%e4%b8%8b%ef%bc%89\/"},"modified":"2023-01-15T21:20:02","modified_gmt":"2023-01-15T13:20:02","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac16%e7%ab%a0-%e5%9f%ba%e4%ba%8enk%e7%bb%86%e8%83%9e%e7%9a%84%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e6%b2%bb%e7%96%97%ef%bc%88%e4%b8%8b%ef%bc%89","status":"publish","type":"post","link":"http:\/\/oncolab.cn\/index.php\/2023\/01\/15\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac16%e7%ab%a0-%e5%9f%ba%e4%ba%8enk%e7%bb%86%e8%83%9e%e7%9a%84%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e6%b2%bb%e7%96%97%ef%bc%88%e4%b8%8b%ef%bc%89\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c16\u7ae0 \u57fa\u4e8eNK\u7ec6\u80de\u7684\u80bf\u7624\u514d\u75ab\u6cbb\u7597\uff08\u4e0b\uff09"},"content":{"rendered":"
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\u4e0a\u671f\u5185\u5bb9\uff1a\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c16\u7ae0 \u57fa\u4e8eNK\u7ec6\u80de\u7684\u80bf\u7624\u514d\u75ab\u6cbb\u7597\uff08\u4e0a\uff09<\/span><\/a><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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16.2.1 KIRs<\/p>\n<\/section>\n

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KIR2DL1\u3001KIR2DL2\u548cKIR2DL3\u662f\u6291\u5236\u6027\u53d7\u4f53\uff0c\u4e0e\u9776\u7ec6\u80de\u4e0a\u7684HLA-C\u7ed3\u5408\u540e\uff0c\u53c2\u4e0e\u8c03\u63a7NK\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u6027\u548c\u7ec6\u80de\u56e0\u5b50\u7684\u4ea7\u751f\u3002KIR\u53d7\u4f53\u5728NK\u7ec6\u80de\u6297\u80bf\u7624\u53cd\u5e94\u4e2d\u7684\u4f5c\u7528\u5728\u63a5\u53d7\u4e86\u5355\u500d\u4f53\u76f8\u5408\u9aa8\u9ad3\u79fb\u690d\u5b9e\u9a8c\u7684\u6025\u6027\u9ad3\u7cfb\u767d\u8840\u75c5\uff08AML\uff09\u60a3\u8005\u4e2d\u5f97\u5230\u4e86\u8bc1\u5b9e\u3002<\/span><\/p>\n

\u4e8b\u5b9e\u4e0a\uff0c\u63a5\u53d7KIR\/HLA-C\u4e0d\u5339\u914d\u9aa8\u9ad3\u79fb\u690d\u7684\u4e9a\u7ec4\u60a3\u8005\u5728\u4e0d\u51fa\u73b0GVHD\uff08\u79fb\u690d\u7269\u6297\u5bbf\u4e3b\u75c5\uff09<\/span>\u7684\u60c5\u51b5\u4e0b\u75be\u75c5\u590d\u53d1\u7387\u663e\u8457\u964d\u4f4e\uff0c\u5728\u540e\u7eed\u7814\u7a76\u4e2d\u4e5f\u8868\u73b0\u51fa\u66f4\u9ad8\u7684\u751f\u5b58\u7387\u3002<\/span>\u8fd9\u8868\u660e\uff0c\u4f9b\u4f53\u6765\u6e90\u7684\u540c\u79cd\u5f02\u4f53\u53cd\u5e94\u6027NK\u7ec6\u80de\u80fd\u591f\u4ecb\u5bfc\u5b89\u5168\u6301\u4e45\u7684\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002<\/p>\n

\u4e3a\u4e86\u7528\u836f\u7269\u6a21\u62df\u8fd9\u79cd\u6cbb\u7597\u7b56\u7565\uff0c\u79d1\u5b66\u5bb6\u7814\u53d1\u4e86\u4e00\u79cd\u963b\u65adHLA-C\u4e0e\u4e09\u79cd\u6291\u5236\u6027KIR\u53d7\u4f53\u7ed3\u5408\u7684\u6cbb\u7597\u6027\u5355\u514b\u9686\u6297\u4f53\uff1a1-7F9\uff0c\u5b83\u662f\u4e00\u79cd\u5b8c\u5168\u7684\u4ebaIgG4\uff0c\u53ef\u589e\u5f3aNK\u7ec6\u80de\u5bf9\u8868\u8fbeHLA-C\u7684\u80bf\u7624\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u6027\u3002\u5176\u7597\u6548\u5df2\u5728\u4f53\u5916\u4f7f\u7528\u7531\u81ea\u4f53\u6216\u5f02\u4f53NK\u7ec6\u80de\u9776\u5411\u60a3\u8005\u6765\u6e90\u7684AML\u7ec6\u80de\uff0c\u4ee5\u53ca\u5728\u4eba\u6e90\u5316\u7684AML\u5c0f\u9f20\u6a21\u578b\u4e2d\u5f97\u5230\u8bc1\u5b9e\u3002<\/span><\/p>\n

\u8be5\u65b9\u6cd5\u7684\u6709\u6548\u6027\u4e5f\u5728\u540c\u57fa\u56e0\u80bf\u7624\u6a21\u578b\u4e2d\u5f97\u5230\u4e86\u9a8c\u8bc1\u3002\u7528\u7279\u5f02\u6027\u5355\u514b\u9686\u6297\u4f53\u963b\u65adLy49C\/I(\u5c0f\u9f20KIR\u7684\u540c\u6e90\u53d7\u4f53)\u53ef\u4ee5\u5728\u4fdd\u7559\u6b63\u5e38\u7ec4\u7ec7\u7684\u540c\u65f6\uff0c\u8bf1\u5bfcNK\u7ec6\u80de\u9009\u62e9\u6027\u6740\u4f24\u80bf\u7624\u7ec6\u80de\u3002\u5176\u4e5f\u5c06\u8fd0\u7528\u4e8e\u6742\u4ea4\u7624\u884d\u751f\u4ea7\u54c1IPH2101\u7684\u4e34\u5e8a\u5f00\u53d1\u3002<\/span>\u591a\u4e2aI\u671f\u4e34\u5e8a\u8bd5\u9a8c\u6d4b\u8bd5\u7ed3\u679c\u8868\u660e\uff0cKIR\u963b\u65ad\u5242\u662f\u5b89\u5168\u7684\uff0c\u4e14\u526f\u4f5c\u7528\u5f88\u5c0f\uff0c\u503c\u5f97\u505a\u8fdb\u4e00\u6b65\u4e34\u5e8a\u7814\u7a76\u3002<\/p>\n

\u968f\u540e\uff0c\u7814\u7a76\u4eba\u5458\u7814\u5236\u51fa\u5177\u6709\u76f8\u540c\u6297\u539f\u7279\u5f02\u6027\u7684\u7a33\u5b9a\u91cd\u7ec4IgG4 \u7684li<\/span>rilumab\uff08\u9488\u5bf9KIR\u7684\u6291\u5236\u6027\u53d7\u4f53\uff0c\u4e3b\u8981\u662fIPH2102\uff0cBMS-986015\uff09\uff0c\u4ee5\u63d0\u9ad8\u5355\u6297\u7684\u7a33\u5b9a\u6027\u548c\u751f\u4ea7\u7684\u53ef\u884c\u6027\u3002<\/p>\n

\u76ee\u524d\u5df2\u5728\u591a\u4e2aI\u671f\u548cII\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u8fdb\u884c\u4e86\u6d4b\u8bd5\uff1a\u4f5c\u4e3a\u8001\u5e74AML\u60a3\u8005\u7684\u7ef4\u6301\u6027\u5355\u4e00\u7597\u6cd5\uff08NCT01687387\uff09\uff0c\u6216\u4e0e\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u4e2d\u7684\u80bf\u7624\u9776\u5411\u5355\u6297\u57c3\u6d1b\u59a5\u73e0\u5355\u6297<\/span>\uff08NCT0225263\uff09\u6216AML\u4e2d\u7684DNA\u4f4e\u7532\u57fa\u5316\u52425-\u6c2e\u6742\u80de\u82f7\uff08NCT0239917\uff09\u6216\u9aa8\u9ad3\u589e\u751f\u5f02\u5e38\u7efc\u5408\u5f81\uff08NCT02599649\uff09\u3001CLL\uff08\u6162\u6027\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\uff09\u4e2d\u7684\u5229\u59a5\u6614\u5355\u6297<\/span>\uff08NCT02481297\uff09\u8054\u5408\u4f7f\u7528\u3002<\/p>\n

\u6709\u8da3\u7684\u662f\uff0c\u4f53\u5916\u548c\u4f53\u5185\u7814\u7a76\u8868\u660e\uff0clir<\/span>ilumab\u53ef\u4ee5\u589e\u52a0\u5229\u59a5\u6614\u5355\u6297\u8bf1\u5bfc\u4ea7\u751f\u7684ADCC\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6700\u8fd1\uff0c\u4e00\u9879II\u671f\u4e34\u5e8a\u7814\u7a76\u6d4b\u8bd5\u4e86lirilumab\u4f5c\u4e3a\u5355\u4e00\u7597\u6cd5\u6cbb\u7597\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u60a3\u8005\u7684\u7597\u6548\uff0c\u8be5\u7814\u7a76\u56e0\u65e0\u660e\u663e\u6cbb\u7597\u6548\u679c\u800c\u63d0\u524d\u7ec8\u6b62\u3002\u4f5c\u8005\u8ba4\u4e3a\uff0c\u8fd9\u53ef\u80fd\u662f\u7531KIR2D+<\/sup>NK\u7ec6\u80de\u7684\u53cd\u5e94\u6027\u964d<\/span>\u4f4e\u5bfc\u81f4\uff0c\u8fd9\u4e9b\u7ec6\u80de\u8868\u9762\u7684KIR2D\u8868\u8fbe\u4f1a\u53d1\u751f\u51cf\u5c11\u3002\u4f46\u662f<\/span>\uff0c\u5728\u5176\u4ed6\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u5c1a\u672a\u68c0\u6d4b\u5230\u8fd9\u79cd\u7269\u8d28\u7684\u51cf\u5c11\uff0c\u6240\u4ee5\u8fd9\u4e00\u731c\u60f3\u4ecd\u6709\u5f85\u8bc1\u5b9e\u3002<\/span>\u8fd9\u4e9b\u7ed3\u679c\u53ef\u80fd\u8868\u660e\uff0c\u81f3\u5c11\u5728\u67d0\u4e9b\u6076\u6027\u80bf\u7624\u4e2d\uff0c\u9700\u8981\u9002\u5e94\u6027\u7684\u6cbb\u7597\u65b9\u6848\uff08\u95f4\u6b47\u6027\u963b\u65ad\uff09\u6216\u4f7f\u7528\u8054\u5408\u6cbb\u7597\u6765\u8bf1\u5bfc\u6709\u6548\u7684\u6297\u80bf\u7624\u53cd\u5e94\u3002<\/p>\n

\u4f8b\u5982\uff0c\u9274\u4e8e\u6297PD-1\u963b\u65ad\u5355\u514b\u9686\u6297\u4f53\u4e34\u5e8a\u8bd5\u9a8c\u7684\u6210\u529f\uff0c\u4ee5\u53ca\u5b83\u4eec\u80fd\u8bf1\u5bfc\u4fc3\u8fdbNK\u7ec6\u80de\u6fc0\u6d3b\u7684\u514d\u75ab\u523a\u6fc0\u6027\u7ec6\u80de\u56e0\u5b50\uff08\u5982IFN\u03b3\uff09\u7684\u80fd\u529b\uff0c\u5728\u4e34\u5e8a\u6cbb\u7597\u4e2d\u8054\u5408\u4f7f\u7528lirilumab\u548cnivolumab\uff0c\u53ef\u4ee5\u5728\u5b9e\u4f53\u7624\uff08NCT01714739\uff09\u548c\u8840\u6db2\u6076\u6027\u80bf\u7624\uff08NCT01592370\uff09\u7684\u6cbb\u7597\u4e2d\u540c\u65f6\u6062\u590dNK\u7ec6\u80de\u53caT\u7ec6\u80de\u7684\u529f\u80fd\u3002\u5728\u665a\u671f\u5b9e\u4f53\u7624\u60a3\u8005\u4e2d\u8fdb\u884c\u7684\u4e24\u4e2aI\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c\u4e0enivolumab\u5355\u4e00\u7597\u6cd5\u76f8\u6bd4\uff0c\u8fd9\u79cd\u8054\u5408\u7597\u6cd5\u6ca1\u6709\u663e\u793a\u51fa\u989d\u5916\u7684\u4e0d\u826f\u53cd\u5e94<\/span>\u3002<\/p>\n

\u6700\u8fd1\uff0c\u4e00\u9879I\u671f\/II\u671f\u8bd5\u9a8c\u8bc1\u660e\u4e86lirilumab\u8054\u5408nivolumab\u7684\u6cbb\u7597\u65b9\u6cd5\u5bf9\u665a\u671f\u5177\u6709\u8010\u836f\u6027\u7684\u5934\u9888\u764c\u60a3\u8005\u7684\u6cbb\u7597\u662f\u6709\u6548\u7684\u3002\u8fd9\u662f\u4e00\u9879\u5355\u7ec4\u4e34\u5e8a\u8bd5\u9a8c<\/span>\uff0c\u867d\u7136\u6ca1\u6709\u5bf9\u7167\u4eba\u7fa4\uff0c\u4f46\u6709\u53ef\u9760\u7684\u5934\u9888\u764c\u5386\u53f2\u5bf9\u7167\u6570\u636e\u6765\u4f5c\u4e3a\u5224\u65ad\u4f9d\u636e\u3002\u8fd9\u9879\u7814\u7a76\u8868\u660e\uff0c\u5934\u9888\u90e8\u764c\u75c7\u60a3\u8005\u5bf9lirilumab\u7684\u8010\u53d7\u6027\u826f\u597d\u3002\u867d\u7136\u6570\u636e\u4ecd\u5728\u8fdb\u884c\u8ddf\u8e2a\u548c\u5b8c\u5584\uff0c\u4f46\u5728\u5355\u7ec4\u4e34\u5e8a\u8bd5\u9a8c\u7684\u5c0f\u7814\u7a76\u80cc\u666f\u4e0b\uff0c\u4ece\u6cbb\u7597\u6548\u679c\u89d2\u5ea6\u89c2\u5bdf\u5230\u7684\u7ed3\u679c\u5341\u5206\u4ee4\u4eba\u9f13\u821e\u3002<\/span>\u57286\u4e2a\u6708\u548c12\u4e2a\u6708\u65f6\uff0c\u4f7f\u7528lirilumab\u548cnivolumab\u8054\u5408\u6cbb\u7597\u7684\u60a3\u8005\u7684\u603b\u751f\u5b58\u7387\u5206\u522b\u4e3a90%\u548c60%\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u53d7\u7f8e\u56fd\u98df\u54c1\u836f\u7269\u7ba1\u7406\u5c40\u6279\u51c6\u7684\u4ec5\u4f7f\u7528nivolumab\u6cbb\u7597\u7684\u60a3\u8005\u7684\u603b\u751f\u5b58\u7387\u5206\u522b\u4e3a55.6%\u548c36%\u3002<\/p>\n

\u8fd9\u4e9b\u521d\u6b65\u4e34\u5e8a\u6570\u636e\u8868\u660e\uff0c\u8054\u5408\u4f7f\u7528lirilumab\u548cnivolumab\u53ef\u4ee5\u6709\u6548\u6cbb\u7597\u5934\u9888\u764c\u60a3\u8005\uff0c\u8fd9\u9879\u6210\u679c\u5728\u67d0\u79cd\u7a0b\u5ea6\u4e0a\u7c7b\u4f3c\u4e8e\u5176\u4ed6\u764c\u75c7\u9002\u5e94\u75c7\u7684\u62a5\u9053\uff0c\u4f8b\u5982\u7528PD-1\u6216CTLA-4\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u6cbb\u7597\u7684\u9ed1\u8272\u7d20\u7624\u3002\u540c\u65f6\uff0c\u8be5\u8bd5\u9a8c\u7ed3\u679c\u53ef\u4ee5\u5e2e\u52a9\u6211\u4eec\u6df1\u5165\u8bc4\u4f30\u514d\u75ab\u76f8\u5173\u751f\u7269\u6807\u5fd7\u7269\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6700\u8fd1\u53d1\u5e03\u4e86\u4e00\u9879\u968f\u673a\u3001\u53cc\u76f2\u3001\u5b89\u6170\u5242\u5bf9\u7167\u7684II\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff08EffiKIR\uff09\u7684\u7ed3\u679c\uff0c\u8be5\u8bd5\u9a8c\u8bc4\u4f30\u4e86lirilumab\u4f5c\u4e3a\u5355\u4e00\u836f\u7269\u5bf9\u8001\u5e74AML \u60a3\u8005\u7684\u7597\u6548\uff08NCT01687387\uff09\u3002\u5c3d\u7ba1\u8be5\u7814\u7a76\u672a\u8fbe\u5230\u4e3b\u8981\u7597\u6548\u7ec8\u70b9<\/span>\uff0c\u4f46\u8bc1\u5b9e\u4e86lirilumab\u4f5c\u4e3a\u5355\u4e00\u7597\u6cd5\u5177\u6709\u5b89\u5168\u6027\u3002\u5177\u4f53\u7684\u8bd5\u9a8c\u5206\u7ec4\u4e3a\uff0c\u4e24\u7ec4\u60a3\u8005\u5728\u4e0d\u540c\u6cbb\u7597\u95f4\u9694\u63a5\u53d7\u4e0d\u540c\u5242\u91cf\uff08\u6bcf3\u4e2a\u67080.1 mg\/kg\u6216\u6bcf4\u54681 mg\/kg\uff09\u7684\u5355\u5242lirilumab\uff0c<\/span>\u800c\u7b2c\u4e09\u7ec4\u60a3\u8005\u63a5\u53d7\u5b89\u6170\u5242\u3002lirilumab\u7ec4\u548c\u5b89\u6170\u5242\u7ec4\u5728\u65e0\u767d\u8840\u75c5\u751f\u5b58\u7387\uff08LFS\uff09<\/span>\u548c\u5176\u4ed6\u7597\u6548\u7ec8\u70b9\u65b9<\/span>\u9762\u5747\u65e0\u7edf\u8ba1\u5b66\u663e\u8457\u5dee\u5f02\u3002\u8bd5\u9a8c\u6bcf\u4e2a\u67081 mg\/kg\u7ec4\u56e0LFS\u4e0e\u5b89\u6170\u5242\u7ec4\u65e0\u660e\u663e\u5dee\u5f02\u800c\u7ec8\u6b62\u3002\u8be5\u8bd5\u9a8c\u7684\u6570\u636e\u5206\u6790\u4ecd\u5728\u8fdb\u884c\u4e2d\uff0c\u540e\u7eed\u5c06\u8fdb\u4e00\u6b65\u5b8c\u6210\u5bf9\u672c\u8bd5\u9a8c\u7ed3\u679c\u7684\u5206\u6790<\/span><\/span>\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u73b0\u5728\u4ecd\u67096\u9879\u6d89\u53calirilumab\u7684\u8bd5\u9a8c\u5728\u8fdb\u884c\u4e2d\uff0c\u8bd5\u9a8c\u6d89\u53ca\u4e00\u7cfb\u5217\u5b9e\u4f53\u764c\u548c\u8840\u6db2\u764c\u9002\u5e94\u75c7\uff0c\u5e76\u4e0e\u5305\u62ecnivolumab\u5728\u5185\u7684\u5176\u4ed6\u836f\u7269\u8054\u5408\u4f7f\u7528<\/span>\uff08\u89c1clinicaltrials.gov\uff09\u3002 <\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

16.2.2 NKG2A<\/p>\n<\/section>\n

\n
\n
\n

NKG2A\u662f\u4e00\u79cd\u7531\u5927\u591a\u6570NK\u7ec6\u80de\u548c\u90e8\u5206\u7ec6\u80de\u6bd2\u6027T\u6dcb\u5df4\u7ec6\u80de\u8868\u8fbe\u7684\u6291\u5236\u6027\u53d7\u4f53\uff0c\u53ef\u8bc6\u522b\u4eba\u7c7b\u7684HLA-E\u5206\u5b50\u548c\u5c0f\u9f20\u7684Qa-1<\/span>\u5206\u5b50\u3002<\/p>\n

\u4e0e\u7ecf\u5178\u7684HLA I\u7c7b\u5206\u5b50\u4e0d\u540c\uff0c50\u201380%\u7684\u5b9e\u4f53\u7624\u6216\u767d\u8840\u75c5\/\u6dcb\u5df4\u7624\u60a3\u8005\u7684HLA-E\u8868\u8fbe\u4fdd\u7559<\/span>\uff0c\u751a\u81f3\u589e\u52a0\u3002\u800c\u4e00\u9879\u9488\u5bf9NSCLC\u7684\u7814\u7a76\u8868\u660e\uff0c\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2dNK\u7ec6\u80de\u7684\u6fc0\u6d3b\u53d7\u4f53\u548cKIR\u8868\u8fbe\u8f83\u4f4e\uff0c\u4f46NKG2A\u7684\u8868\u8fbe\u4e0d\u53d7\u5f71\u54cd\u3002\u540c\u65f6\uff0cHLA-E\u5728\u80bf\u7624\u7ec6\u80de\u4e0a\u9ad8\u8868\u8fbe\uff0c\u5728\u5468\u56f4\u4e0a\u76ae\u7ec6\u80de\u4e0a\u5448\u9634\u6027\u3002<\/p>\n

NKG2A\u5728\u80bf\u7624\u6d78\u6da6\u7684NK\u7ec6\u80de\u548cT\u7ec6\u80de\u4e0a\u7684\u8868\u8fbe\u4e5f\u5df2\u5728\u4e73\u817a\u764c\u548c\u5bab\u9888\u764c\u4e2d\u5f97\u5230\u8bc1\u5b9e\uff0c\u5e76\u4e14\u4f3c\u4e4e\u4e0e\u80bf\u7624\u7ec6\u80de\u5206\u6ccc\u7684IL-15\u548cTGF-\u03b2\u6709\u5173\u3002\u4e00\u9879\u9488\u5bf9\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684\u7814\u7a76\u8868\u660e\uff0c\u8868\u8fbeNKG2A\u7684\u80bf\u7624\u6297\u539f\u7279\u5f02\u6027CD8+<\/sup>T\u7ec6\u80de\u7684\u6548\u5e94\u5668\u529f\u80fd\u53d7\u5230\u5176\u6291\u5236\u3002<\/p>\n

\u56e0\u6b64\uff0c\u53ea\u6709\u5728\u80bf\u7624\u7a33\u5b9a\u8868\u8fbe\u7ecf\u5178HLA I\u7c7b\u5206\u5b50\u4e14\u4e0d\u8868\u8fbeHLA-E\u7684\u60a3\u8005\u4e2d\uff0c\u80bf\u7624\u6d78\u6da6\u6027CD8+<\/sup>T\u7ec6\u80de\u624d\u662fNSCLC\u60a3\u8005\u7684\u6709\u5229\u9884\u540e\u56e0\u7d20\u3002\u6b64\u5916\uff0cHLA-E\u8868\u8fbe\u589e\u52a0\uff08\u572820%\u7684\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u4e2d\u6709\u8bb0\u5f55\uff09\u4f1a\u9020\u6210\u673a\u4f53\u51fa\u73b0\u5927\u91cfCD8+<\/sup>T\u7ec6\u80de\u6d78\u6da6\u7684\u4e0d\u826f\u540e\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u6240\u6709\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0cNKG2A\u662f\u4e00\u4e2a\u91cd\u8981\u7684\u68c0\u67e5\u70b9\uff0c\u53ef\u4ee5\u76f4\u63a5\u4f5c\u7528\u4e8e\u6d78\u6da6\u7684\u6dcb\u5df4\u7ec6\u80de\uff0c\u53ef\u4ee5\u901a\u8fc7\u963b\u65ad\u5b83\u6765\u63d0\u9ad8\u673a\u4f53\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002\u5728\u4e00\u9879\u4e34\u5e8a\u524d\u8bd5\u9a8c\u4e2d\uff0c\u4e00\u79cd\u9488\u5bf9NKG2A\uff08Z270\uff09\u7684\u4eba\u6e90\u5316\u5355\u6297\u5728\u4f53\u5185\u548c\u4f53\u5916\u8bd5\u9a8c\u4e2d\u90fd\u8868\u73b0\u51fa\u4e86\u53ef\u4ee5\u6709\u6548\u589e\u5f3a<\/span>NK\u7ec6\u80de\u5bf9\u767d\u8840\u75c5\u548c\u6dcb\u5df4\u7624\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u6027\u3002\u8fd9\u79cd\u6297\u4f53\u540e\u6765\u88ab\u5f00\u53d1\u8fd0\u7528\u4e8e\u4e34\u5e8a\u6cbb\u7597\uff0c\u540d\u4e3a\u83ab\u90a3\u5229\u73e0\u5355\u6297\uff08IPH\uff09\u3002<\/p>\n

\u76ee\u524d\uff0c\u5b83\u4f5c\u4e3a\u5355\u4e00\u836f\u7269\u8fd0\u7528\u4e8e\u5987\u79d1\u6076\u6027\u80bf\u7624\u7684II\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff08NCT02459301\uff09\u3001\u53e3\u8154\u9cde\u72b6\u7ec6\u80de\u764c\u7684\u672f\u524d\u6cbb\u7597\uff08NCT02331875\uff09\uff0c\u6216\u4e0e\u897f\u59a5\u6614\u5355\u6297<\/span>\uff08\u6297EGFR\u5355\u6297\uff09\u8054\u5408\u6cbb\u7597\u5934\u9888\u764c\uff08NCT02643550\uff09\u3001\u4e0e\u4f0a\u5e03\u66ff\u5c3c\uff08BTK\u6291\u5236\u5242\uff09\u8054\u5408\u6cbb\u7597CLL\uff08NCT02557516\uff09\u3001\u4e0e\u675c\u74e6\u9c81\u5355\u6297\uff08\u6297PD-L1\u5355\u6297\uff09\u8054\u5408\u6cbb\u7597\u5404\u79cd\u5b9e\u4f53\u7624\uff08NCT02671435\uff09\u3002 <\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

16.2.3 PD1<\/p>\n<\/section>\n

\n
\n
\n

PD-1\u662f\u4e00\u79cd\u7ed3\u5408PD-L1\u548cPD-L2\u7684\u6291\u5236\u6027\u53d7\u4f53\uff0cPD-L1\u548cPD-L2\u7684\u7279\u5f02\u6027\u914d\u4f53\u8868\u8fbe\u4e8e\u591a\u4e2a\u80bf\u7624\u6216\u611f\u67d3\u7ec6\u80de\u4e0a\uff0c\u4e5f\u8868\u8fbe\u4e8e\u708e\u75c7\u7076\u4e2d\u7684\u4e13\u804c\u6297\u539f\u5448\u9012\u7ec6\u80de\uff08APC\uff09\u3002<\/p>\n

\u7814\u7a76\u8005\u6700\u65e9\u662f\u5728T\u3001B\u548c\u9ad3\u6837\u7ec6\u80de\u4e0a\u53d1\u73b0PD-1\u7684\u8868\u8fbe\uff0c\u800c\u6700\u8fd1\u6709\u7814\u7a76\u53d1\u73b0\u5728\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u548c\u5375\u5de2\u764c\u60a3\u8005\u7684NK\u7ec6\u80de\u4e0a\u4e5f\u5b58\u5728PD-1\u7684\u8868\u8fbe<\/span>\u3002\u4f53\u5916\u7814\u7a76\u8868\u660e\uff0cNK\u7ec6\u80de\u4e0aPD-1\u4e0e\u80bf\u7624\u7ec6\u80de\u8868\u8fbe\u7684PD-L1\u7ed3\u5408\u4f1a\u6291\u5236NK\u7ec6\u80de\u5bf9\u80bf\u7624\u7ec6\u80de\u7684\u6740\u4f24\u80fd\u529b\uff0c<\/span>\u800cPD-1\u963b\u65ad\u5355\u6297\u53ef\u4ee5\u6062\u590dNK\u7ec6\u80de\u529f\u80fd\uff0c\u4fc3\u8fdbNK\u7ec6\u80de\u5411\u80bf\u7624\u90e8\u4f4d\u8fc1\u79fb\u3002<\/p>\n

\u5728\u8fc7\u53bb\u51e0\u5e74\u4e2d\uff0c\u5df2\u7ecf\u5f00\u53d1\u51fa\u51e0\u79cd\u963b\u65adPD1\/PD-L1\u76f8\u4e92\u4f5c\u7528\u7684\u6297\u4f53\uff08Table.16.1<\/span>\uff09\uff0c\u76ee\u524d\u5df2\u7528\u4e8e\u6cbb\u7597\u665a\u671f\u5b9e\u4f53\u7624\u3002\u5176\u4e2d\uff0cnivolumab\u5df2\u88ab\u8bc1\u660e\u80fd\u5728T\u6dcb\u5df4\u7ec6\u80de\u4e2d\u8bf1\u5bfc\u4e0e\u7ec6\u80de\u6bd2\u4f5c\u7528\u3001NK\u7ec6\u80de\u529f\u80fd\u76f8\u5173\u57fa\u56e0\u7684\u8868\u8fbe\uff0c\u5982IFN\u03b3\u548c\u9897\u7c92\u9176B\u3002\u8fd9\u4e9b\u6570\u636e\u8868\u660e\uff0c\u5728T\u7ec6\u80de\u548cNK\u7ec6\u80de\u4e2d\uff0c\u6297PD-1\/PD-L1\u5355\u6297\u53ef\u4ee5\u901a\u8fc7\u76f8\u540c\u7684\u5206\u5b50\u673a\u5236\u6765\u63d0\u9ad8\u673a\u4f53\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002<\/span><\/p>\n

\u5728\u5c0f\u9f20\u4f53\u5185\u8fdb\u884c\u7684PD-1\u963b\u65ad\u8bd5\u9a8c\u4e2d\uff0c\u53ef\u4ee5\u89c2\u5bdf\u5230\u5c0f\u9f20\u673a\u5185\u51fa\u73b0\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u6062\u590d\u7684\u73b0\u8c61\u3002\u540c\u65f6\uff0c\u5728\u5b9e\u4f53\u764c\u548c\u8840\u6db2\u764c\u60a3\u8005\u4e2d\u8fdb\u884c\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e0a\uff0c\u4e5f\u53ef\u4ee5\u89c2\u5bdf\u5230\u8fd0\u7528\u6297PD-1\/PD-L1\u5355\u6297\u7684\u5355\u4e00\u7597\u6cd5\u5bf9\u75be\u75c5\u7684\u6cbb\u7597\u662f\u6709\u6548\u7684\uff0c\u5b83\u53ef\u4ee5\u523a\u6fc0\u673a\u4f53\u51fa\u73b0\u6709\u5229\u7684\u4e34\u5e8a\u53cd\u5e94\u3002<\/span>\u91cd\u8981\u7684\u662f\uff0c\u8fd9\u4e9b\u53cd\u5e94\u901a\u5e38\u662f\u6301\u4e45\u7684\uff0c\u4e14\u5bf9\u5927\u591a\u6570\u4eba\u6ca1\u6709\u4e25\u91cd\u6bd2\u6027\u3002\u53ea\u6709\u5c11\u6570\u4f7f\u7528PD-1\u6216PD-L1\u7279\u5f02\u6027\u6297\u4f53\u6cbb\u7597\u7684\u60a3\u8005\u4f1a\u51fa\u73b0\u5f3a\u70c8\u7684\u4e0d\u826f\u53cd\u5e94\u3002<\/p>\n

\u4f7f\u7528\u8be5\u7597\u6cd5\u65f6\u80bf\u7624\u7684\u5feb\u901f\u51cf\u5c11\u7387<\/span>\u901a\u5e38\u572810%\u523040%\u4e4b\u95f4\uff0c\u5177\u4f53\u901f\u7387\u53d6\u51b3\u4e8e\u60a3\u8005\u81ea\u8eab\u3002\u4e3a\u4e86\u89e3\u91ca\u8fd9\u79cd\u53d8\u5f02\u6027\uff0c\u4ece\u7ec4\u7ec7\u5b66\u89d2\u5ea6\u5bf9\u6cbb\u7597\u524d\u4ece\u60a3\u8005\u5904\u6536\u96c6\u5230\u7684\u5404\u79cd\u80bf\u7624\u6d3b\u68c0\u8fdb\u884c\u4e86\u68c0\u67e5\uff0c\u5176\u7ec4\u6210\u4e0e\u5728\u60a3\u8005\u89c2\u5bdf\u5230\u7684\u53cd\u5e94\u7b49\u7ea7\u6709\u5173\u3002<\/span><\/p>\n

\u68c0\u67e5\u7ed3\u679c\u660e\u786e\u4e86\u5bf9\u6297PD-L1\/PD-1\u7597\u6cd5\u6709\u53cd\u5e94\u7684\u4e09\u79cd\u514d\u75ab\u7279\u5f81\u8868\u578b<\/span>\u3002<\/span>\u7b2c\u4e00\u4e2a\u7279\u5f81\u662f\u201c\u708e\u75c7\u201d\u8868\u578b\uff0c\u5176\u7279\u5f81\u662f\u5728\u80bf\u7624\u5b9e\u8d28\u4e2d\uff0c\u80bf\u7624\u7ec6\u80de\u5468\u56f4\u5b58\u5728\u5927\u91cf\u514d\u75ab\u7ec6\u80de\u3002\u5728\u8fd9\u4e9b\u6837\u672c\u4e2d\uff0c\u6d78\u6da6\u7684\u514d\u75ab\u7ec6\u80de\u53ef\u80fd\u8868\u73b0\u51faPD-L1\u67d3\u8272\u3002\u8fd9\u4e00\u7279\u5f81\u8868\u660e\u673a\u4f53\u9884\u5148\u5b58\u5728\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\uff0c\u4f46\u8be5\u53cd\u5e94\u53ef\u80fd\u5df2\u88ab\u80bf\u7624\u4e2d\u7684\u514d\u75ab\u6291\u5236\u6240\u963b\u904f\u3002\u4e8b\u5b9e\u4e0a\uff0c\u6297PD-L1\/PD-1\u5355\u6297\u5728\u4e34\u5e8a\u4e0a\u6700\u5e38\u7528\u4e8e\u708e\u75c7\u578b\u80bf\u7624\u60a3\u8005\u7684\u6cbb\u7597\uff0c\u5e76\u4e14\u6cbb\u7597\u6548\u679c\u663e\u8457\u3002<\/p>\n

\u7b2c\u4e8c\u4e2a\u7279\u5f81\u662f\u201c\u514d\u75ab\u6392\u65a5\u201d\u8868\u578b\uff0c\u5176\u7279\u5f81\u4e5f\u662f\u5b58\u5728\u5927\u91cf\u514d\u75ab\u7ec6\u80de\uff0c\u4f46\u5b83\u4eec\u4f4d\u4e8e\u80bf\u7624\u7ec6\u80de\u5468\u56f4\u7684\u57fa\u8d28\u4e2d\uff0c\u4e0d\u7a7f\u900f\u5b9e\u8d28\u3002<\/p>\n

\u7b2c\u4e09\u79cd\u662f\u201c\u514d\u75ab\u6c99\u6f20\u201d\u8868\u578b\uff0c\u5176\u7279\u5f81\u662f\u80bf\u7624\u7684\u5b9e\u8d28\u6216\u57fa\u8d28\u4e2d\u7f3a\u4e4f\u9020\u8840\u7ec6\u80de\u3002\u8fd9\u79cd\u8868\u578b\u53ef\u80fd\u53cd\u6620\u4e86\u673a\u4f53\u5b58\u5728\u6297\u80bf\u7624\u514d\u75ab\u7f3a\u5931\uff0c\u56e0\u6b64\u8fd9\u7c7b\u80bf\u7624\u60a3\u8005\u5bf9\u6297PD-L1\/PD-1\u7597\u6cd5\u4e0d\u4ea7\u751f\u53cd\u5e94\u4e5f\u5c31\u4e0d\u8db3\u4e3a\u5947\u4e86\u3002<\/p>\n

\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u5e76\u975e\u6240\u6709\u5177\u6709\u514d\u75ab\u708e\u75c7\u7279\u5f81\u7684\u80bf\u7624\u90fd\u5bf9\u6297PD-L1\/PD-1\u6cbb\u7597\u6709\u53cd\u5e94\u3002\u5728\u8fd9\u4e9b\u60c5\u51b5\u4e0b\uff0c\u6211\u4eec\u8003\u8651\u662f\u5426\u5176\u4ed6\u514d\u75ab\u68c0\u67e5\u70b9\u624d\u662f\u6291\u5236\u673a\u4f53\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u7684\u539f\u56e0\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

16.2.4 LAG3<\/p>\n<\/section>\n

\n
\n
\n

\u6dcb\u5df4\u7ec6\u80de\u6d3b\u5316\u57fa\u56e03\uff0c\u53c8\u79f0LAG3\uff0c\u662f\u4e00\u79cd\u5c5e\u4e8e\u514d\u75ab\u7403\u86cb\u767d\u8d85\u5bb6\u65cf\u7684\u7ec6\u80de\u8868\u9762\u5206\u5b50\uff0c\u7531\u6d3b\u5316\u7684T\u6dcb\u5df4\u7ec6\u80de\u3001NK\u7ec6\u80de\u3001B\u7ec6\u80de\u548c\u6d46\u7ec6\u80de\u6837\u6811\u7a81\u72b6\u7ec6\u80de\u8868\u8fbe\uff0c\u5177\u6709\u591a\u79cd\u751f\u7269\u5b66\u6548\u5e94\u3002<\/p>\n

LAG3\u662fMHC II\u7c7b\u5206\u5b50\u7684\u914d\u4f53\uff0c\u5b83\u4e0eMHC II\u7c7b\u5206\u5b50\u7ed3\u5408\u65f6\u5177\u6709\u5f88\u9ad8\u7684\u4eb2\u548c\u529b\u3002\u5b83\u662f\u4e00\u79cd\u514d\u75ab\u68c0\u67e5\u70b9\u53d7\u4f53\uff0c\u8d1f\u6027\u8c03\u8282T\u7ec6\u80de\u7684\u7ec6\u80de\u589e\u6b96\u3001\u6fc0\u6d3b\u548c\u5185\u73af\u5883\u7a33\u6001\uff0c\u636e\u62a5\u9053\u5b83\u53ef\u4ee5\u6fc0\u6d3bTreg\u7684\u6291\u5236\u529f\u80fd\u3002<\/span><\/p>\n

\u5728\u53d1\u73b0LAG3\u65e9\u671f\uff0cLAG3\u7f3a\u9677\u5c0f\u9f20\u7684\u5b9e\u9a8c\u8868\u660e\uff0cLAG3\u5728NK\u7ec6\u80de\u4e2d\u53d1\u6325\u7740\u81f3\u5173\u91cd\u8981\u7684\u4f5c\u7528\u3002<\/span>\u4f46\u662f\uff0c\u7531\u4e8eLAG3\u4e5f\u88ab\u53d1\u73b0\u5728\u80bf\u7624\u6d78\u6da6\u7684CD8+<\/sup>T\u7ec6\u80de\u4e0a\u8868\u8fbe\uff0c\u5e76\u6291\u5236\u5176\u589e\u6b96\u548cIFN\u03b3\u7684\u4ea7\u751f\uff0c\u56e0\u6b64\uff0c\u9488\u5bf9LAG3\u7684\u7814\u7a76\u4e3b\u8981\u96c6\u4e2d\u5728\u5176\u6297\u4f53<\/span>\u5728\u8c03\u8282\u9002\u5e94\u6027\u514d\u75ab\u4e2d\u7684\u4f5c\u7528\u3002<\/p>\n

LAG3\u73b0\u5728\u662f\u5236\u836f\u516c\u53f8\u5f00\u53d1\u9488\u5bf9\u764c\u75c7\u548c\u81ea\u8eab\u514d\u75ab\u75c5\u65b0\u7597\u6cd5\u7684\u5404\u79cd\u836f\u7269\u7684\u4e3b\u8981\u76ee\u6807\u9776\u70b9\u3002<\/span>LAG3\u7279\u5f02\u6027\u5355\u514b\u9686\u6297\u4f53\u7684\u9884\u671f\u4f5c\u7528\u673a\u5236\u662f\u89e3\u9664NK\u7ec6\u80de\u548cT\u7ec6\u80de\u7684\u8d1f\u8c03\u8282\u3002<\/p>\n

MHC II\u7c7b\u5206\u5b50\u901a\u5e38\u4ec5\u7531APC\u8868\u8fbe\uff0c\u4f46\u636e\u62a5\u9053\u4e00\u4e9b\u764c\u7ec6\u80de\u4e5f\u4f1a\u8868\u8fbe\u5b83\u4eec\u3002\u7814\u7a76\u8868\u660e\uff0cLAG3\u4e0e\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u8868\u8fbe\u7684MHC II\u7c7b\u5206\u5b50\u7684\u76f8\u4e92\u4f5c\u7528\u53ef\u4ee5\u4fdd\u62a4\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u514d\u53d7FAS<\/span>\u4ecb\u5bfc\u7684\u7ec6\u80de\u51cb\u4ea1\u3002<\/p>\n

LAG3\u8fd8\u7f16\u7801\u53e6\u4e00\u79cd\u526a\u63a5\u53d8\u4f53\uff0c\u8be5\u53d8\u4f53\u53ef\u8f6c\u5316\u4e3a\u53ef\u6eb6\u6027LAG3\uff08sLAG3\uff09\uff0c\u5177\u6709\u514d\u75ab\u4f50\u5242\u6d3b\u6027\u3002\u5c3d\u7ba1\u4fc3\u8fdbLAG3\u7f16\u7801sLAG3\u4e0d\u662f\u4f7f\u7528LAG3\u7279\u5f02\u6027\u5355\u514b\u9686\u6297\u4f53\u8fdb\u884c\u4e34\u5e8a\u8bd5\u9a8c\u7684\u9884\u671f\u76ee\u6807\uff0c\u4f46\u5176\u53ef\u80fd\u6709\u5229\u4e8e\u60a3\u8005\u6cbb\u7597\u3002<\/span><\/p>\n

\u6709\u8da3\u7684\u662f\uff0csLAG3\u88ab\u8ba4\u4e3a\u53ea\u4e0eAPC\u4e00\u5c0f\u90e8\u5206\u8102\u7b4f\u5fae\u7ed3\u6784\u57df\u4e2d\u7684MHC II\u7c7b\u5206\u5b50\u7ed3\u5408\u3002\u540c\u6837\u6709\u8da3\u7684\u662f\uff0c\u4e00\u79cd\u4e34\u5e8a\u7ea7\u53ef\u6eb6\u6027LAG3\u86cb\u767d\uff08LAG3-Ig\u878d\u5408\u86cb\u767d\uff0cIMP321\uff09\uff0c\u540c\u65f6\u4e5f\u662f\u4e00\u79cd\u751f\u7406\u6027\u9ad8\u4eb2\u548c\u529bMHC II\u7c7b\u5206\u5b50\u7c98\u5408\u5242\uff0c\u5df2\u88ab\u8bc1\u660e\u5728\u77ed\u671f\u4f53\u5916\u8bd5\u9a8c\u4e2d\u53ef\u4ee5\u8bf1\u5bfcNK\u7ec6\u80de\u548cCD8+<\/sup>T\u7ec6\u80de\u4ea7\u751fIFN\u03b3\u548cTNF\u3002IMP321\u7684I\u671f\u548cII\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4ecd\u5728\u8fdb\u884c\uff0c\u5176\u5206\u522b\u4f5c\u4e3a\u6807\u51c6\u5316\u7597\u7684\u8f85\u52a9\u7597\u6cd5\u6216\u8054\u5408\u6297PD-1\u6cbb\u7597\u7684\u514d\u75ab\u523a\u6fc0\u836f\u7269\u3002BMS-986016\u662f\u4e00\u79cd\u6297LAG3\u5355\u514b\u9686\u6297\u4f53\uff0c\u76ee\u524d\u6b63\u5728\u8fdb\u884cII\u671f\u4e34\u5e8a\u8bd5\u9a8c\u3002<\/p>\n

\u8bb8\u591a\u5176\u4ed6LAG3\u6297\u4f53\u4ecd\u5728\u4e34\u5e8a\u524d\u7814\u7a76\u4e2d\uff0c\u6709\u5f85\u8fdb\u4e00\u6b65\u53d1\u6398\u3002<\/span>LAG3\u53ef\u80fd\u662f\u6bd4PD-1\u66f4\u597d\u7684\u68c0\u67e5\u70b9\u6291\u5236\u5242\u9776\u70b9\uff0c\u56e0\u4e3a\u5b83\u65e2\u80fd\u6fc0\u6d3bT\u7ec6\u80de\u548cNK\u6548\u5e94\u7ec6\u80de\uff0c\u53c8\u80fd\u6291\u5236Treg\u6291\u5236\u6d3b\u6027\u3002\u9488\u5bf9LAG3\u8054\u5408nivolumab\uff08NCT01968109\uff09\u7684\u6cbb\u7597\u7b56\u7565\u76ee\u524d\u6b63\u5728\u7814\u7a76\u4e2d\uff0c\u53d7\u8bd5\u8005\u4e3a\u5c40\u90e8\u665a\u671f\uff08\u8f6c\u79fb\u6027\u548c\/\u6216\u4e0d\u53ef\u5207\u9664\u7684\uff09\u5b9e\u4f53\u7624\u60a3\u8005\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

16.2.5 Tim-3<\/p>\n<\/section>\n

\n
\n
\n

Tim-3\u662f\u4e00\u79cd\u7531\u5148\u5929\u6027\u548c\u9002\u5e94\u6027\u514d\u75ab\u7ec6\u80de\u8868\u8fbe\u7684I\u578b\u7cd6\u86cb\u767d\u3002\u5b83\u9996\u5148\u88ab\u9274\u5b9a\u4e3a\u5728\u4ea7\u751fIFN\u03b3\u7684CD4+<\/sup>T\u8f85\u52a9\u7ec6\u80de1\uff08Th1\uff09\u548cCD8+<\/sup>\u7ec6\u80de\u6bd2\u6027T\u7ec6\u80de\u4e0a\u9009\u62e9\u6027\u8868\u8fbe\u7684\u5206\u5b50\u3002\u540c\u65f6\u5b83\u4e5f\u662f\u529f\u80fd\u6210\u719f\u7684NK\u7ec6\u80de\u7ec4\u6210\u6027\u8868\u8fbe\u7684\u5206\u5b50\u3002<\/span>Tim-3\u5728\u88ab\u6fc0\u6d3b\u540e\uff0c\u901a\u8fc7\u964d\u4f4e\u7ec6\u80de\u6bd2\u6027\u548c\u4ea7\u751f\u7ec6\u80de\u56e0\u5b50\uff0c\u6765\u4f5c\u4e3aNK\u548cT\u7ec6\u80de\u7684\u6291\u5236\u6027\u53d7\u4f53\u53d1\u6325\u4f5c\u7528\u3002<\/p>\n

\u5728\u665a\u671f\u9ed1\u8272\u7d20\u7624\u3001NSCLC\u548c\u6ee4\u6ce1\u6027B\u7ec6\u80de\u975e\u970d\u5947\u91d1\u6dcb\u5df4\u7624\u60a3\u8005\u7684T\u7ec6\u80de\u4e0a\u4e5f\u53d1\u73b0\u6709Tim-3\u3002\u5728\u8fd9\u4e09\u79cd\u764c\u75c7\u4e2d\uff0c\u6240\u6709Tim-3+<\/sup>T\u7ec6\u80de\u5171\u540c\u8868\u8fbePD-1\uff0c\u5e76\u8868\u73b0\u51fa\u589e\u6b96\u548c\u7ec6\u80de\u56e0\u5b50\u4ea7\u751f\u7f3a\u9677\u7684\u7279\u70b9\u3002<\/p>\n

\u6700\u8fd1\u7684\u4e00\u9879\u7814\u7a76\u8868\u660e\uff0c\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u5faa\u73afNK\u7ec6\u80de\u4e2dTim-3\u7684\u8868\u8fbe\u589e\u52a0\uff0c\u5e76\u51fa\u73b0\u4e86\u8870\u7aed\u8868\u578b\u3002\u56e0\u6b64\uff0c\u7528\u5355\u514b\u9686\u6297\u4f53\u963b\u65adTim-3\u4fe1\u53f7\u53ef\u4ee5\u4fc3\u8fdb\u80ba\u817a\u764c\u60a3\u8005\u5916\u5468NK\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u6027\u548cIFN\u03b3\u4ea7\u751f\u589e\u52a0\u3002\u56e0\u6b64\uff0cNK\u7ec6\u80de\u4e2dTim-3\u7684\u8868\u8fbe\u53ef\u4ee5\u4f5c\u4e3a\u4eba\u7c7b\u6076\u6027\u80bf\u7624\u7684\u9884\u540e\u751f\u7269\u6807\u5fd7\u7269\u3002<\/p>\n

\u6297Tim-3\u963b\u65ad\u5355\u514b\u9686\u6297\u4f53\u76ee\u524d\u6b63\u5728\u8fdb\u884cI\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u5373\u5c06\u516c\u5e03\u7684\u8bc1\u636e\u8868\u660e\uff0c\u5b83\u4eec\u53ef\u4e0e\u6297PD-1\u7597\u6cd5\u7ed3\u5408\u4f7f\u7528\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5728\u4e34\u5e8a\u8fd0\u7528\u6297PD-1\u6cbb\u7597\u7684\u80cc\u666f\u4e0b\uff0c\u6cbb\u7597\u5931\u8d25\u4e0e\u66ff\u4ee3\u514d\u75ab\u68c0\u67e5\u70b9\uff08\u6700\u663e\u8457\u7684\u662fTim-3\uff09\u7684\u4e0a\u8c03\u76f8\u5173\uff0c\u800c\u5f53\u6297Tim-3\u5355\u514b\u9686\u6297\u4f53\u4e0e\u6297PD-1\u836f\u7269\u4e00\u8d77\u4f7f\u7528\u65f6\uff0c\u53ef\u4ee5\u6709\u6548\u51cf\u5c11\u60a3\u8005\u5bf9\u6297PD-1\u6cbb\u7597\u7684\u8010\u836f\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

16.2.6 TIGIT<\/p>\n<\/section>\n

\n
\n
\n

TIGIT\uff08T\u7ec6\u80de\u514d\u75ab\u7403\u86cb\u767d\u548cITIM\u7ed3\u6784\u57df\uff09\u662f\u514d\u75ab\u7403\u86cb\u767d\u8d85\u5bb6\u65cf\u7684\u4e00\u79cd\u53d7\u4f53\uff0c\u5728NK\u7ec6\u80de\u3001\u6548\u5e94\u548c\u8bb0\u5fc6T\u7ec6\u80de\u4ee5\u53caTreg\u7ec6\u80de\u4e0a\u8868\u8fbe\uff0c\u5728\u8fd9\u4e9b\u7ec6\u80de\u4e0a\uff0c\u5b83\u4f5c\u4e3a\u4e00\u79cd\u5171\u6291\u5236\u53d7\u4f53\u53d1\u6325\u4f5c\u7528\u3002<\/p>\n

\u5b83\u7ed3\u5408\u7684\u4e24\u79cd\u914d\u4f53CD155\uff08PVR\uff09\u548cCD112\uff08PVRL2\uff0cnectin-2\uff09\uff0c\u5728APC\u3001T\u7ec6\u80de\u548c\u5305\u62ec\u80bf\u7624\u7ec6\u80de\u5728\u5185\u7684\u591a\u79cd\u975e\u9020\u8840\u7ec6\u80de\u4e0a\u8868\u8fbe\u3002<\/p>\n

CD226\uff08DNAM-1\uff09\u7684\u914d\u4f53\u4e0eTIGIT\u76f8\u540c\uff0c\u4f46\u5176\u4eb2\u548c\u529b\u8f83\u4f4e\u3002\u91cd\u8981\u7684\u662f\uff0cTIGIT\u53ef\u4ee5\u6291\u5236CD226\u548cCD155\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u3002TIGIT\u53c2\u4e0e\u8bf1\u5bfcCD226\u78f7\u9178\u5316\u548cSHP1\uff08\u542b\u6709SH2\u7ed3\u6784\u57df\u7684\u808c\u9187-5-\u78f7\u9178\u91761\uff09\u7684\u52df\u96c6\uff0c\u5e76\u5bfc\u81f4NK\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u6027\u3001\u9897\u7c92\u6781\u5316\u548c\u7ec6\u80de\u56e0\u5b50\u5206\u6ccc\u53d7\u5230\u6291\u5236\u3002<\/p>\n

\u5728\u4e0e\u80bf\u7624\u7ec6\u80de\u4e0a\u9ad8\u5ea6\u8868\u8fbe\u7684CD155\u548cCD112\u76f8\u4e92\u4f5c\u7528\u540e\uff0cTIGIT\u8d1f\u5411\u8c03\u8282\u6297\u80bf\u7624\u53cd\u5e94\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5728\u4e24\u79cd\u4e0d\u540c\u7684\u80bf\u7624\u6a21\u578b\u4e2d\uff0cTIGIT\u7f3a\u9677\u5c0f\u9f20\u7684\u80bf\u7624\u751f\u957f\u51fa\u73b0\u660e\u663e\u5ef6\u8fdf\uff0c\u800cTIGIT\u5728\u5e7f\u6cdb\u7684\u80bf\u7624\u6d78\u6da6\u6dcb\u5df4\u7ec6\u80de\u4e0a\u9ad8\u5ea6\u8868\u8fbe\u3002<\/p>\n

\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684CD8+<\/sup>T\u7ec6\u80de\u4e2d\uff0cTIGIT\u4e0ePD-1\u8054\u5408\u963b\u65ad\u53ef\u8fdb\u4e00\u6b65\u6539\u5584\u7ec6\u80de\u589e\u6b96\u3001\u7ec6\u80de\u56e0\u5b50\u7684\u4ea7\u751f\u53ca\u8131\u9897\u7c92\u3002\u5728\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\uff0c\u8be5\u8054\u5408\u7597\u6cd5\u53ef\u80fd\u4f1a\u5bfc\u81f4\u673a\u4f53\u5bf9\u80bf\u7624\u4ea7\u751f\u5b8c\u5168\u6392\u65a5\u53cd\u5e94\u3002<\/p>\n

\u6709\u8da3\u7684\u662f\uff0cTIGIT\u4e0d\u4ec5\u80fd\u4e0ePD-1\u534f\u540c\u4f5c\u7528\uff0c\u8fd8\u80fd\u4e0eTim-3\u534f\u540c\u4f5c\u7528\uff0c\u524a\u5f31\u673a\u4f53\u6297\u80bf\u7624\u53cd\u5e94\u3002\u56e0\u6b64\uff0cTIGIT\u4e0ePD-1\u6216TIGIT\u4e0eTim-3\u8054\u5408\u963b\u65ad\u53ef\u4fc3\u8fdb\u6297\u80bf\u7624\u514d\u75ab\u5e76\u8bf1\u5bfc\u80bf\u7624\u6d88\u9000\u3002\u4e00\u79cd\u4eba\u7c7b\u6297TIGIT\u5355\u514b\u9686\u6297\u4f53\uff08MTIG7192A\uff0cRG6058\uff09\u4e0e\u6297PD-1\u7597\u6cd5\u8054\u5408\u5e94\u7528\u4e8e\u5404\u79cd\u5b9e\u4f53\u7624\u7684I\u671f\u4e34\u5e8a\u8bd5\u9a8c\u6b63\u5728\u8fdb\u884c\u4e2d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n


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

\n
\n

16.3  Perspectives<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
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\u6700\u8fd1\u5728\u80bf\u7624\u6cbb\u7597\u65b9\u9762\u7684\u7a81\u7834\u662f\u79d1\u5b66\u5bb6\u51e0\u5341\u5e74\u6765\u7684\u7814\u7a76\u7684\u6210\u679c\uff0c\u5b83\u53ef\u4ee5\u5e2e\u52a9\u6211\u4eec\u66f4\u597d\u5730\u7406\u89e3\u764c\u75c7\u7684\u751f\u7269\u5b66\u57fa\u7840\uff0c\u91ca\u653e\u514d\u75ab\u7cfb\u7edf\u7684\u529b\u91cf\u3002<\/span><\/p>\n

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\u53ea\u6709\u901a\u8fc7\u5bf9\u4f53\u5185\u80bf\u7624\u8fdb\u884c\u6d3b\u4f53\u7ec4\u7ec7\u68c0\u67e5\uff0c\u786e\u5b9a\u6700\u6709\u53ef\u80fd\u5bf9\u963b\u65ad\u4e0d\u540c\u514d\u75ab\u6291\u5236\u6027\u53d7\u4f53\u7684\u9776\u5411\u6cbb\u7597\u65b9\u6848\u6709\u53cd\u5e94\u7684\u60a3\u8005\uff0c\u624d\u80fd\u51b3\u5b9a\u9488\u5bf9\u80bf\u7624\u548c\u60a3\u8005\u7684\u9776\u5411\u6cbb\u7597\u65b9\u6848\u3002<\/span><\/p>\n<\/section>\n<\/section>\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><\/p>\n


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\u2014 THE  END \u2014<\/span><\/p>\n


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\u6765\u6e90 | Oncoimmunology: A Practical Guide <\/span><\/section>\n
for Cancer Immunotherapy<\/span><\/section>\n
\u4f5c\u8005 | Laura Chiossone and Eric Vivier<\/span><\/section>\n
\u7ffb\u8bd1 |   \u90ed\u5b50 \u848b\u4fca\u535a \u7f57\u4f73\u4f73<\/span><\/span><\/section>\n
\u7f16\u8f91\u6392\u7248 | \u8d75\u6db5<\/span><\/span><\/section>\n
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\u7f51\u5740\u662f\uff1aoncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u7f51\u5740\u662f\uff1adh.<\/strong><\/span>oncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u8be5\u661f\u7403\u7528\u4e8eOncoLab\u516c\u4f17\u53f7\u8bfb\u8005\u4ea4\u6d41\u5b66\u4e60\u4f7f\u7528\uff0c\u6c38\u4e45\u514d\u8d39<\/span>\u3002<\/span><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\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":"

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