{"id":4386,"date":"2022-05-03T00:00:00","date_gmt":"2022-05-02T16:00:00","guid":{"rendered":"http:\/\/dh.oncolab.cn\/index.php\/2022\/05\/03\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac8%e7%ab%a0%ef%bc%9a%e5%85%8d%e7%96%ab%e6%8a%91%e5%88%b6%e7%bd%91%e7%bb%9c%e4%b8%ad%e6%b5%86%e7%bb%86%e8%83%9e%e6%a0%b7dc%e5%92%8c%e8%b0%83-2\/"},"modified":"2022-05-03T00:00:00","modified_gmt":"2022-05-02T16:00:00","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac8%e7%ab%a0%ef%bc%9a%e5%85%8d%e7%96%ab%e6%8a%91%e5%88%b6%e7%bd%91%e7%bb%9c%e4%b8%ad%e6%b5%86%e7%bb%86%e8%83%9e%e6%a0%b7dc%e5%92%8c%e8%b0%83-2","status":"publish","type":"post","link":"http:\/\/dh.oncolab.cn\/index.php\/2022\/05\/03\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac8%e7%ab%a0%ef%bc%9a%e5%85%8d%e7%96%ab%e6%8a%91%e5%88%b6%e7%bd%91%e7%bb%9c%e4%b8%ad%e6%b5%86%e7%bb%86%e8%83%9e%e6%a0%b7dc%e5%92%8c%e8%b0%83-2\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c8\u7ae0\uff1a\u514d\u75ab\u6291\u5236\u7f51\u7edc\u4e2d\u6d46\u7ec6\u80de\u6837DC\u548c\u8c03\u8282\u6027T\u7ec6\u80de\u7684\u4f5c\u7528\uff08\u4e0b\uff09"},"content":{"rendered":"
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\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c8\u7ae0\uff1a\u514d\u75ab\u6291\u5236\u7f51\u7edc\u4e2d\u6d46\u7ec6\u80de\u6837DC\u548c\u8c03\u8282\u6027T\u7ec6\u80de\u7684\u4f5c\u7528\uff08\u4e0a\uff09<\/a>\u7684\u5185\u5bb9\u53ef\u70b9\u51fb\u94fe\u63a5\u67e5\u770b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.2.2 pDC\u4ecb\u5bfc\u7684Treg\u589e\u6b96<\/strong><\/p>\n<\/section>\n

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\u9ad8TATreg<\/sub>\u6c34\u5e73\u662f\u5f71\u54cdBT(\u539f\u53d1\u6027\u4e73\u817a\u80bf\u7624)\u60a3\u8005\u751f\u5b58\u9884\u540e\u4e0d\u826f\u7684\u72ec\u7acb\u56e0\u7d20\u3002\u6b64\u5916\uff0cBT\u6d78\u6da6\u7684CD4+<\/sup>FoxP3neg<\/sup> T\u7ec6\u80de(TATconv)\u5177\u6709\u8bb0\u5fc6\u6027\u8868\u578b(CD45RO+<\/sup>)\uff0c\u4e0e\u9ad8\u5ea6\u6d3b\u5316\u7684TATreg<\/sub>(ICOShigh<\/sup>\u3001CTLA-4+<\/sup>\u3001GITR+<\/sup>\u3001HLA-DR+<\/sup>)\u76f8\u6bd4\uff0c\u5f88\u5c11\u88ab\u6fc0\u6d3b(Ki67+) \u5e76\u5728\u4f53\u5916\u663e\u793a\u6291\u5236\u6d3b\u6027\u3002<\/p>\n

\u6b64\u5916\uff0c\u5728\u9ed1\u8272\u7d20\u7624\u548c\u5375\u5de2\u80bf\u7624\u4e2d\uff0c\u5c5e\u4e8eCD28\u5bb6\u65cf\u7684ICOS\u5728TATreg<\/sub>\u4e2d\u9ad8\u8868\u8fbe\uff0c\u5c3d\u7ba1TATreg<\/sub>\u539f\u4f4d\u8868\u8fbeKi67\uff0c\u4f46TATreg<\/sub>\u5728\u7ecf\u5178\u7684\u6297CD3\/\u6297CD28\u6fc0\u52a8\u5242Ab\u5305\u88ab\u7684\u5fae\u7403\u523a\u6fc0\u4e0b\u4ee5\u53ca\u5728\u5916\u6e90\u6027IL-2\u5b58\u5728\u7684\u60c5\u51b5\u4e0b\uff0c\u4e0d\u80fd\u5728\u4f53\u5916\u589e\u6b96\uff0c\u8fd9\u4e0eBT\u6216\u8840\u6db2\u4e2d\u5f3a\u70c8\u589e\u6b96\u7684\u8840\u6db2Treg<\/sub>\u6216Tconv\u5f62\u6210\u4e86\u9c9c\u660e\u7684\u5bf9\u6bd4\u3002<\/p>\n

\u91cd\u8981\u7684\u662f\uff0cpDC\u5bf9BT\u7684\u6d78\u6da6\u4e5f\u4e0eTreg<\/sub>\u6d78\u6da6\u4ee5\u53ca\u80bf\u7624\u5185\u3001\u5c24\u5176\u662fTNBT\u5185\u5171\u540c\u5b9a\u4f4d\u7684\u4e24\u4e2a\u7ec6\u80de\u4e9a\u7fa4\u76f8\u5173\uff0c\u60a3\u8005\u7684\u751f\u5b58\u9884\u540e\u4e5f\u5f88\u5dee\u3002\u56e0\u6b64\uff0c\u6211\u4eec\u60f3\u77e5\u9053TApDC\u662f\u5426\u53ef\u80fd\u6709\u52a9\u4e8eTATreg<\/sub>\u5728BT\u5fae\u73af\u5883\u4e2d\u7684\u6269\u589e\u3002<\/p>\n

\u6211\u4eec\u89c2\u5bdf\u5230\uff0cTApDC\u548c\u7ecfBT\u57f9\u517b\u4e0a\u6e05\u9884\u5904\u7406\u7684\u5065\u5eb7\u4f9b\u8005\u7684pDC\u5728\u8bf1\u5bfcFoxp3+<\/sup>Treg<\/sub>\u9009\u62e9\u6027\u6269\u589e\u4ee5\u53ca\u8bf1\u5bfc\u5206\u6cccIL-10\u7684CD4+<\/sup>T\u7ec6\u80de\u7684\u5206\u5316\u65b9\u9762\u975e\u5e38\u6709\u6548\u3002\u6709\u8da3\u7684\u662f\uff0c\u5916\u6e90\u6027 IFN-\u03b1 \u9006\u8f6c\u4e86\u7531 TApDC \u548c BT \u73af\u5883\u8bf1\u5bfc\u7684\u514d\u75ab\u6291\u5236\u6027 CD4+ T \u7ec6\u80de\u53cd\u5e94\uff0c\u8fd9\u8868\u660e\u5728\u80bf\u7624\u4e2d IFN-\u03b1 \u7684\u4ea7\u751f\u53d7\u635f\u53ef\u5bfc\u81f4TApDC \u7684\u4fc3\u80bf\u7624\u80fd\u529b\u589e\u5f3a\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u4e3a\u4e86\u4e86\u89e3TApDC\u7684\u8d1f\u9762\u5f71\u54cd\uff0c\u6211\u4eec\u5efa\u7acb\u4e86\u4e00\u4e2a\u4e0e\u4eba\u7c7b\u75c5\u7406\u975e\u5e38\u63a5\u8fd1\u7684\u539f\u4f4d\u5c0f\u9f20\u4e73\u817a\u80bf\u7624\u6a21\u578b\uff0c\u5305\u62ecpDC\u548cTreg<\/sub>\u6d78\u6da6\u3002\u6211\u4eec\u53d1\u73b0TApDC\u5927\u591a\u662f\u672a\u6210\u719f\u7684\uff0c\u5728\u4f53\u5185\u4fdd\u6301\u5176\u5185\u5316\u6297\u539f\u7684\u80fd\u529b\uff0c\u5e76\u5728\u4f53\u5916\u4fdd\u6301\u5176\u6fc0\u6d3bCD4+<\/sup>T\u7ec6\u80de\u7684\u80fd\u529b\u3002<\/p>\n

\u66f4\u91cd\u8981\u7684\u662f\uff0cTApDC\u5728\u4f53\u5916\u5bf9\u4f5c\u4e3aTLR9\u914d\u4f53\u7684\u7ec6\u80de\u56e0\u5b50\u53ef\u4ea7\u751f\u6709\u7279\u5f02\u6027\u7684\u6539\u53d8\uff0c\u800c\u5bf9TLR7\u914d\u4f53\u7684\u53cd\u5e94\u4fdd\u6301\u4e0d\u53d8\u3002\u5728\u4f53\u5185\uff0cpDC\u7684\u7f3a\u5931\u5ef6\u7f13\u4e86\u80bf\u7624\u7684\u751f\u957f\uff0c\u964d\u4f4e\u4e86\u80bf\u7624\u5185Treg<\/sub>\u7684\u6bd4\u4f8b\uff0c\u8fd9\u8868\u660eTApDC\u63d0\u4f9b\u4e86\u4e00\u4e2a\u514d\u75ab\u6291\u5236\u7684\u73af\u5883\uff0c\u5f88\u53ef\u80fd\u662f\u901a\u8fc7\u6fc0\u6d3bTreg<\/sub>\u4fc3\u8fdb\u4e86\u80bf\u7624\u7684\u751f\u957f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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pDC\u5148\u524d\u88ab\u8bc1\u660e\u53ef\u8c03\u8282\u591a\u53d1\u6027\u9aa8\u9ad3\u7624(MM)\u7ec6\u80de\u7684\u751f\u957f\uff0c\u6700\u8fd1\u88ab\u8bc1\u660e\u6709\u5229\u4e8e\u4e73\u817a\u764c\u7ec6\u80de\u7684\u9aa8\u8f6c\u79fb\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5065\u5eb7\u4f9b\u8005\u7684pDC\u5728TLR7\u6216TLR9\u6fc0\u52a8\u5242\u4f53\u5916\u6fc0\u6d3b\u540e\u9ad8\u8868\u8fbeICOS-L\uff0c\u800c\u5c3d\u7ba1TApDC\u5176\u8868\u578b\u4e3aCD40+<\/sup>HLA-DR+<\/sup>CD86+<\/sup>\uff0c\u4f46\u5728\u4e73\u817a\u548c\u5375\u5de2\u80bf\u7624\u6269\u589e\u4e2d\u7f3a\u4e4fICOS-L\u7684\u8868\u8fbe\u3002<\/p>\n

\u6709\u8da3\u7684\u662f\uff0c\u5728\u4f53\u5916\uff0cICOS+<\/sup>CD4+<\/sup>T\u7ec6\u80de\u4e0eICOS-L\u7684\u7ed3\u5408\u4f1a\u5bfc\u81f4\u5176\u5728pDC\u819c\u4e0a\u7684\u8868\u8fbe\u4e0b\u8c03\uff0c\u800c\u5728\u963b\u65ad\u6027\u6297ICOS\u5355\u6297\u5b58\u5728\u7684\u60c5\u51b5\u4e0b\uff0c\u80bf\u7624\u7ec6\u80de\u6269\u589e\u60ac\u6db2\u57f9\u517b24\u5c0f\u65f6\u540e\uff0cTApDC\u4e0aICOS-L\u7684\u8868\u8fbe\u6062\u590d\u3002<\/p>\n

\u8fd9\u4e9b\u6570\u636e\u8868\u660e\uff0c\u5728Treg<\/sub>\/pDC\u63a5\u89e6\u8fc7\u7a0b\u4e2d\uff0cBT\u4e2d\u53d1\u751f\u4e86ICOS\/ICOS-L\u7684\u76f8\u4e92\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6709\u8da3\u7684\u662f\uff0c[pDC+<\/sup>TA-CD4+<\/sup>T\u7ec6\u80de]\u5171\u57f9\u517b\u7684\u540c\u79cd\u5f02\u4f53\u53cd\u5e94\u5bfc\u81f4\u4e86FoxP3+<\/sup>Treg<\/sub>\u7684\u5f3a\u70c8\u5bcc\u96c6\u548c\u589e\u6b96\uff0c\u5e76\u4fc3\u8fdb\u4e86IL-10\u7684\u5206\u6ccc\u3002\u8fd9\u79cd\u514d\u75ab\u6291\u5236T\u7ec6\u80de\u5bf9pDC\u523a\u6fc0\u7684\u53cd\u5e94\u9ad8\u5ea6\u4f9d\u8d56\u4e8eICOS\uff0c\u56e0\u4e3a\u52a0\u5165\u4e2d\u548c\u7684\u6297ICOS\u5355\u6297\u53ef\u4ee5\u9009\u62e9\u6027\u5730\u6291\u5236Treg<\/sub>\u589e\u6b96\u548cIL-10\u7684\u5206\u6ccc\u3002<\/p>\n

\u6b64\u5916,\u9ad3\u7cfbDC (mDC, Linneg<\/sup>HLA-DR+ <\/sup>CD11c+ <\/sup>BDCA2neg<\/sup>)\u5728\u6fc0\u6d3b\u540e\u4e0d\u8fc7\u5ea6\u8868\u8fbeICOS-L\uff0c\u4e0eTreg<\/sub>\u5bcc\u96c6\u6216\u5f3a\u70c8\u5206\u6cccIL-10\u65e0\u5173\u3002\u4e0e\u6211\u4eec\u5bf9TATreg<\/sub>\u7684\u89c2\u5bdf\u4e00\u81f4\u7684\u662f\u5375\u5de2\u80bf\u7624\u8179\u6c34\u4e2d\u7684ICOS+<\/sup>Treg<\/sub>\u6216\u80f8\u817a\u4e2d\u8868\u8fbeICOS\u7684\u81ea\u7136Treg<\/sub>(nTreg<\/sub>)\u5bf9pDC\u7684\u53cd\u5e94\u4e5f\u4f9d\u8d56\u4e8eICOS\/ICOS-L\u7684\u76f8\u4e92\u4f5c\u7528\u3002<\/p>\n

\u6b64\u5916\uff0cpDC\u8fd8\u88ab\u62a5\u9053\u901a\u8fc7ICOS\/ICOSL\u76f8\u4e92\u4f5c\u7528\u589e\u52a0CD4 T\u7ec6\u80de\u5bf9IL-10\u7684\u4ea7\u751f\u3002\u6b64\u5916\uff0c\u6211\u4eec\u6700\u8fd1\u4e0eD Olive\u56e2\u961f\u5408\u4f5c\uff0c\u8bc1\u5b9e\u4e86\u5728\u4f53\u5185ICOS-L\u5bf9\u6ee4\u6ce1\u6027\u6dcb\u5df4\u7624B\u7ec6\u80de\u7684\u4e0b\u8c03\uff0c\u4ee5\u53caICOS\/ICOS-L\u4f9d\u8d56\u6027\u7684Treg<\/sub>\u5728\u8fd9\u79cd\u80bf\u7624\u73af\u5883\u4e2d\u7684\u6269\u5f20\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u91cd\u8981\u7684\u662f\uff0c\u4e0eIL-10\u76f8\u53cd\uff0c\u5728BT\u4e2d\u65e2\u6ca1\u6709\u68c0\u6d4b\u5230IL-2\u3001IL-17\uff0c\u4e5f\u6ca1\u6709\u68c0\u6d4b\u5230IFN-\u03b3\u3002ICOS\u7684\u4e2d\u548c\u4ec5\u8f7b\u5fae\u964d\u4f4e\u4e86TFN-\u03b1\u7684\u5206\u6ccc\u548cTconv\u7684\u589e\u6b96\uff0c\u5e76\u4e0d\u5f71\u54cdT\u7ec6\u80de\u5bf9mDC\u7684\u5e94\u7b54\u3002\u8fd9\u8868\u660eICOS\u6709\u5229\u4e8eTATreg<\/sub>\u7684\u6269\u589e\u548cIL-10\u7684\u4ea7\u751f\uff0c\u4f46\u4e0d\u53c2\u4e0e\u539f\u53d1BT\u514d\u75ab\u6548\u5e94\u7684\u8bf1\u5bfc\u3002\u6700\u91cd\u8981\u7684\u662f\uff0c\u5728\u4e00\u7ec4BT\u60a3\u8005\u7684\u56de\u987e\u6027\u961f\u5217\u4e2d\uff0cIHC\u68c0\u6d4b\u5230ICOS\u4e3b\u8981\u5728Treg<\/sub>\u4e0a\u8868\u8fbe\uff0c\u5728\u5355\u53d8\u91cf\u5206\u6790\u4e2d\uff0cICOS+<\/sup>\u7ec6\u80de\u6d78\u6da6\u4e0ePFS\u548cOS\u51cf\u5c11\u76f8\u5173\uff0c\u8fd9\u4e0e\u5375\u5de2\u80bf\u7624\u7684\u7ed3\u679c\u4e00\u81f4\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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ICOS\u6784\u6210\u4f53\u6db2\u514d\u75ab\u53cd\u5e94\u7684\u5173\u952e\u8c03\u8282\u56e0\u5b50\uff0c\u4e3b\u8981\u662f\u56e0\u4e3a\u5b83\u523a\u6fc0\u6ee4\u6ce1\u8f85\u52a9T\u7ec6\u80de(Tfh)\u6fc0\u6d3b\uff0c\u5982ICOS\u7f3a\u9677\u5c0f\u9f20\u548c\u60a3\u8005\u6240\u8868\u73b0\u7684\u90a3\u6837\u3002\u4e00\u4e9b\u62a5\u544a\u4e5f\u8868\u660eICOS\u53ef\u80fd\u6709\u52a9\u4e8e\u6297\u80bf\u7624\u7ec6\u80de\u514d\u75ab\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c\u5df2\u7ecf\u5728\u5bf9\u6297CTLA-4(Ipilimumab)\u6cbb\u7597\u6709\u53cd\u5e94\u7684\u60a3\u8005\u4e2d\u89c2\u5bdf\u5230\u4ea7\u751fIFN-\u03b3\u7684CD4+<\/sup>ICOS+<\/sup>T\u7ec6\u80de\u7684\u6bd4\u4f8b\u589e\u52a0\uff0c\u800cICOS\u7f3a\u9677\u5c0f\u9f20\u5bf9\u643a\u5e26B16\u80bf\u7624\u7684\u6297CTLA-4\u6cbb\u7597\u6ca1\u6709\u8fbe\u5230\u9884\u671f\u6cbb\u7597\u6548\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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ICOS+<\/sup>Treg<\/sub>\u5df2\u5728\u51e0\u79cd\u4eba\u548c\u5c0f\u9f20\u80bf\u7624\u4e2d\u88ab\u62a5\u9053\uff0c\u6211\u4eec\u7684\u4f53\u5916\u5b9e\u9a8c\u8868\u660eICOS+<\/sup>TATreg<\/sub>\u7684\u6269\u589e\u5f3a\u70c8\u4f9d\u8d56ICOS\uff0c\u800c\u4e0d\u662f\u6765\u81ea\u5916\u5468\u8840\u7684Treg<\/sub>\u3002ICOS\u4f9d\u8d56\u6027\u53ef\u4ee5\u53cd\u6620\u8fd9\u79cdTreg<\/sub>\u7684\u7279\u5b9a\u4e9a\u7fa4\uff0c\u6216\u8005\u4e0e\u80f8\u817aICOS+<\/sup>nTreg<\/sub>\u7c7b\u4f3c\u7684\u7279\u5b9a\u6765\u6e90\u76f8\u5173\u8054\uff0c\u6216\u8005\u4e0e\u5176\u5fae\u73af\u5883\u6216\u6fc0\u6d3b\u72b6\u6001\u76f8\u5173\u8054\u3002\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\uff0c\u76ee\u524d\u8fd8\u4e0d\u6e05\u695aTATreg<\/sub>\u662fnTreg<\/sub>\u8fd8\u662f\u7531\u5916\u5468\u5e7c\u7a1a\u7684T\u7ec6\u80de\u8bf1\u5bfc\u7684\u3002\u4ece\u9006\u8f6c\u4e73\u817a\u764c\u60a3\u8005TACD4+<\/sup>T\u7ec6\u80de\u514d\u75ab\u6291\u5236\u53cd\u5e94\u7684\u89d2\u5ea6\u6765\u770b\uff0c\u4e86\u89e3ICOS\u963b\u65ad\u662f\u5426\u5728nTreg<\/sub>\u3001iTreg<\/sub>\u548cTATreg<\/sub>\u4e4b\u95f4\u663e\u793a\u51fa\u4e0d\u540c\u7684\u5f71\u54cd\u53ef\u80fd\u662f\u81f3\u5173\u91cd\u8981\u7684\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u7efc\u4e0a\u6240\u8ff0\uff0c\u6211\u4eec\u7684\u6570\u636e\u8868\u660e\uff0cICOS\u963b\u65ad\u53ef\u80fd\u662f\u4e00\u79cd\u5f88\u6709\u524d\u666f\u7684\u6cbb\u7597\u7b56\u7565\uff0c\u53ef\u4ee5\u6839\u9664\u539f\u53d1\u6027BT\u4e2d\u4ea7\u751fTATreg<\/sub>\u548cIL-10\u7684CD4+<\/sup>T\u7ec6\u80de\u3002ICOS\u7684\u4e2d\u548c\u53ef\u80fd\u9700\u8981\u662f\u6682\u65f6\u7684\uff0c\u4ee5\u4fbf\u5728\u4e0d\u5e72\u6270\u53ef\u80fd\u8868\u8fbeICOS\u7684\u6548\u5e94\u7ec6\u80de\u6062\u590d\u7684\u540c\u65f6\u6765\u6d88\u9664Treg<\/sub>\u7684\u6269\u589e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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8.2.2.1  \u7ed3\u8bba<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\n

\u603b\u4e4b\uff0c\u6211\u4eec\u7684\u7ed3\u679c\u663e\u793aBT\u5fae\u73af\u5883\u901a\u8fc7TGF-\u03b2\u548cTNF-\u03b1\u6291\u5236TApDC\u4ea7\u751fI\u578b\u5e72\u6270\u7d20\uff0c\u4ece\u800c\u589e\u5f3a\u4e86\u5b83\u4eec\u5728\u4f53\u5185\u901a\u8fc7ICOS-ICOSL\u76f8\u4e92\u4f5c\u7528\u4fc3\u8fdbFoxP3\u9ad8\u8868\u8fbeTATreg<\/sub>\u6269\u589e\u548cIL-10\u5206\u6ccc\u7684T\u7ec6\u80de\u7684\u80fd\u529b\u3002<\/p>\n

\u8fd9\u6709\u5229\u4e8e\u514d\u75ab\u6291\u5236\u6027\u7684CD4+<\/sup>T\u7ec6\u80de\u5728\u80bf\u7624\u90e8\u4f4d\u7684\u805a\u96c6\uff0c\u963b\u6b62\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94(Fig.8.4<\/span>)\u3002\u6211\u4eec\u7684\u89c2\u5bdf\u7ed3\u679c\u4e3a\u4e73\u817a\u764c\u60a3\u8005\u7684\u65b0\u6cbb\u7597\u7b56\u7565\u7684\u5f00\u53d1\u94fa\u5e73\u4e86\u9053\u8def\uff0c(1)\u901a\u8fc7\u5c06TLR7\/9\u914d\u4f53\u4e0eTNF-\u03b1\u548cTGF-\u03b2\u62ee\u6297\u5242\u7ed3\u5408\u4f7f\u7528\uff0c\u6062\u590dTApDC\u7684IFN-\u03b1\u7684\u4ea7\u751f\uff0c\u4ece\u800c\u8bf1\u5bfc\u6709\u6548\u7684\u6297\u75c5\u6bd2\u6837\u6297\u80bf\u7624\u514d\u75ab\uff0c\u6216(2)\u4e2d\u548cpDC\u548cTreg<\/sub>\u4e4b\u95f4\u7684ICOS\/ICOS-L\u76f8\u4e92\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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Fig 8.4 <\/span>\u4f4d\u4e8e\u4e73\u817a\u80bf\u7624\u514d\u75ab\u6291\u5236\u7f51\u7edc\u4e2d\u5fc3\u7684pDC\/Treg<\/sub>\uff0cICOS\/ICOSL\u7684\u4f5c\u7528\u3002BT\u548cICOS+<\/sup>\u7ec6\u80de\u901a\u8fc7TApDC\u8868\u8fbeICOS-L\u53c2\u4e0eTreg<\/sub>\u7684\u589e\u6b96\u548cIL-10\u7684\u5206\u6ccc\uff0c\u4e0e\u60a3\u8005\u7684\u4e0d\u826f\u9884\u540e\u6709\u5173\u3002\u8fd9\u8868\u660eICOS\u53c2\u4e0e\u4e86T\u7ec6\u80de\u4ecb\u5bfc\u7684\u514d\u75ab\u6291\u5236\uff0c\u63d0\u793a\u4e2d\u548cTreg\u4e0a\u7684ICOS\u662f\u4e00\u79cd\u65b0\u7684\u80bf\u7624\u514d\u75ab\u6cbb\u7597\u7b56\u7565\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n

8.2.3 Treg\u4ecb\u5bfc\u7684\u6291\u5236\u4f5c\u7528<\/strong><\/p>\n<\/section>\n

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Treg<\/sub>\u80fd\u6291\u5236\u5927\u591a\u6570\u514d\u75ab\u7ec6\u80de\uff0c\u5305\u62ecCD4+<\/sup>\u548cCD8+<\/sup>T\u7ec6\u80de\u3001DC\u3001B\u7ec6\u80de\u3001M\u03a6\u548cNK\u7ec6\u80de\u3002\u4f53\u5185\u548c\u4f53\u5916\u7814\u7a76\u8868\u660e\uff0cTreg<\/sub>\u4ecb\u5bfc\u7684\u6291\u5236\u53ef\u4ee5\u901a\u8fc7\u591a\u79cd\u673a\u5236\u53d1\u6325\u4f5c\u7528\uff0c\u5e76\u4e14\u4e0d\u540c\u7684\u5206\u5b50\u53ef\u4ee5\u5728\u7ec6\u80de\u8868\u9762\u5206\u6ccc\u6216\u8868\u8fbe\uff0c\u5e76\u540c\u65f6\u534f\u540c\u5730\u79ef\u6781\u53c2\u4e0e\u5b83\u4eec\u5bf9\u8fd9\u4e9b\u4e0d\u540c\u7ec6\u80de\u4e9a\u7fa4\u7684\u6291\u5236\u529f\u80fd(Fig.8.5<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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


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

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Fig8.5<\/span> Treg<\/sub>\u6291\u5236\u673a\u5236\u3002\u8be5\u793a\u610f\u56fe\u63cf\u8ff0\u4e86\u56db\u79cd\u4e0d\u540c\u6a21\u5f0f\u7684Treg<\/sub>\u6291\u5236\u673a\u5236\u3002<\/p>\n

\u201c\u6291\u5236\u6027\u7ec6\u80de\u56e0\u5b50\u201d\u5305\u62ecIL-10\u3001IL-35\u548cTGF-\u03b2\u3002<\/p>\n

\u201c\u7ec6\u80de\u6eb6\u89e3\u201d\u5305\u62ec\u9897\u7c92\u9176A\u548c\u9897\u7c92\u9176B\u4f9d\u8d56\u7684\u6740\u4f24\u673a\u5236\u548c\u7a7f\u5b54\u7d20\u4f9d\u8d56\u7684\u6740\u4f24\u673a\u5236\u3002<\/p>\n

\u201c\u4ee3\u8c22\u7d0a\u4e71\u201d\u5305\u62ec\u9ad8\u4eb2\u548c\u529bIL-2\u53d7\u4f53\u03b1(CD25)\u4f9d\u8d56\u7684\u7ec6\u80de\u56e0\u5b50\u5265\u593a\u4ecb\u5bfc\u7684\u7ec6\u80de\u51cb\u4ea1\uff0c\u73af\u78f7\u9178\u817a\u82f7(cAMP)\u4ecb\u5bfc\u7684\u6291\u5236\uff0c\u4ee5\u53caCD39\u548c\/\u6216CD73\u4ea7\u751f\u7684\u817a\u560c\u5464\u80fd\u817a\u82f7\u53d7\u4f53(A2A)\u4ecb\u5bfc\u7684\u514d\u75ab\u6291\u5236\u3002<\/p>\n

\u201c\u9776\u5411\u6811\u7a81\u72b6\u7ec6\u80de\u201d\u5305\u62ec\u8c03\u8282DC\u6210\u719f\u6216\u529f\u80fd\u7684\u673a\u5236\uff0c\u5982LAG3(\u4e5f\u79f0\u4e3aCD223)-MHC-II\u4ecb\u5bfc\u7684\u6291\u5236DC\u6210\u719f\u7684\u673a\u5236\uff0c\u4ee5\u53caCTLA4-CD80\/CD86\u4ecb\u5bfc\u7684\u8bf1\u5bfcDC\u5432\u54da\u80fa2\uff0c3-\u53cc\u52a0\u6c27\u9176(IDO)\u4ea7\u751f\u7684\u673a\u5236\uff0cIDO\u662f\u4e00\u79cd\u514d\u75ab\u6291\u5236\u9176\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

IL2<\/span>\uff1aIL-2\u53ef\u80fd\u901a\u8fc7STAT5\u4e0a\u8c03FOXP3\u7684\u8868\u8fbe\uff0c\u589e\u5f3aTreg<\/sub>\u6291\u5236\u529f\u80fd\u3002\u6b64\u5916\uff0cTreg<\/sub>\u8fd8\u53ef\u4ee5\u901a\u8fc7\u5176\u9ad8\u4eb2\u548c\u529b\u7684IL-2R\u03b1\u53d7\u4f53(CD25R)\u901a\u8fc7\u6d88\u8017\u6765\u5265\u593a\u5c40\u90e8\u7684IL-2\u3002<\/p>\n

\u7ec6\u80de\u56e0\u5b50\u5206\u6ccc<\/span>\uff1aIL-10\u548cTGF-\u03b2\u53c2\u4e0enTreg<\/sub>\u548ciTreg<\/sub>\u4ecb\u5bfc\u7684\u6291\u5236\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u9897\u7c92\u9176\u4f9d\u8d56\u6027\u7ec6\u80de\u6eb6\u89e3<\/span>\uff1a\u4eba\u7c7bTreg<\/sub>\u8868\u8fbe\u7a7f\u5b54\u7d20\u548c\u6fc0\u6d3b\u9897\u7c92\u9176A\u540e,\u53ef\u4ee5\u6740\u6b7bCD4+<\/sup>\u548cCD8+<\/sup>T\u7ec6\u80de\u548c\u5176\u4ed6\u72ec\u7acb\u4e8eFas\u548cFasL\u7684\u7ec6\u80de\u7c7b\u578b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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CD39\u548cCD73\u4ecb\u5bfc\u7684\u7ec6\u80de\u5916\u6838\u82f7\u9178\u4ee3\u8c22<\/span>\uff1aCD73\u4e0eCD39\u534f\u540c\u4f5c\u7528\uff0c\u4eceATP\u4ea7\u751f\u817a\u82f7(ADO)\u3002CD39\u4e3b\u8981\u50ac\u5316ATP\u8f6c\u5316\u4e3aAMP\uff0cAMP\u88abCD73\u964d\u89e3\u751f\u6210\u817a\u82f7\u3002\u4e3a\u4e86\u4ecb\u5bfc\u6291\u5236\uff0cADO\u4e0e\u56db\u4e2a\u4e0d\u540c\u7684ADAR\u4e4b\u4e00(A1\u3001A2A\u3001A2B\u3001A3)\u7ed3\u5408\u3002A2A\u548cA2B\u53d7\u4f53\u5076\u8054\u5230Gs\u4e9a\u57fa\u4e0a\uff0c\u6fc0\u6d3b\u817a\u82f7\u9178\u73af\u5316\u9176\u548c\u86cb\u767d\u6fc0\u9176A(PKA)\uff0c\u4ece\u800c\u63d0\u9ad8cAMP\u6c34\u5e73\u3002\u5148\u5929\u514d\u75ab\u7ec6\u80de\u548c\u83b7\u5f97\u6027\u514d\u75ab\u7ec6\u80de\u4e0eA2B\u548cA2A\u7684\u7ed3\u5408\u6291\u5236\u4e86\u5b83\u4eec\u529f\u80fd\u3002<\/p>\n

\u4e8b\u5b9e\u4e0a\uff0c\u817a\u82f7\u901a\u8fc7A2B\u53d7\u4f53\u5f71\u54cdAPC(\u5355\u6838\u7ec6\u80de\u548cDC)\u7684\u6210\u719f\u53ca\u5176\u4fc3\u708e\u7ec6\u80de\u56e0\u5b50\u7684\u5206\u6ccc\uff0c\u5e76\u901a\u8fc7\u8bf1\u5bfc\u5355\u6838\u7ec6\u80de\u5206\u6cccIL-10\u800c\u4fc3\u8fdb\u514d\u75ab\u6291\u5236\u73af\u5883\u7684\u5f62\u6210\u3002<\/p>\n

\u6b64\u5916\uff0c\u817a\u82f7\u53ef\u901a\u8fc7A2A\u53d7\u4f53\u964d\u4f4eNK\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u529b\uff0c\u51cf\u5c11IFN-\u03b3\u7684\u5206\u6ccc\uff0c\u4fc3\u8fdb\u514d\u75ab\u6291\u5236\u7ec6\u80de\u56e0\u5b50(IL-4\u548cTGF-\u03b2)\u7684\u5206\u6ccc\uff0c\u6291\u5236BCR\u8bf1\u5bfc\u7684NF-\u03baB\u6d3b\u5316\uff0c\u964d\u4f4e\u6548\u5e94T\u7ec6\u80de\u7684\u4e3b\u8981\u529f\u80fd\uff0c\u5982IL-2\u548cIFN-\u03b3\u7684\u5206\u6ccc\u3001\u589e\u6b96\u548c\u7ec6\u80de\u6eb6\u89e3\u529f\u80fd\uff0c\u5e76\u6539\u53d8\u5176\u5b58\u6d3b\u7387\u3002\u817a\u82f7\u901a\u8fc7\u8fd9\u4e9b\u9014\u5f84\u5171\u540c\u5f71\u54cd\u4e86\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u7684\u6548\u679c\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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CD39\u548cCD73\u5171\u540c\u5c06ATP\u964d\u89e3\u4e3a\u817a\u82f7\uff0c<\/span>\u662fTreg<\/sub>\u8bf1\u5bfc\u7ec6\u80de\u5468\u56f4\u817a\u82f7\u4ea7\u751f\u7684\u4e00\u79cd\u673a\u5236\u3002\u7136\u800c\uff0c\u867d\u7136\u5927\u591a\u6570\u7814\u7a76\u62a5\u9053CD39\u548cCD73\u5728\u5c0f\u9f20Treg<\/sub>\u4e0a\u5171\u8868\u8fbe\uff0c\u4f46\u6211\u4eec\u7684\u5de5\u4f5c\u8868\u660e\uff0c\u5728\u4eba\u7684\u5916\u5468\u8840\u6db2\u3001\u6dcb\u5df4\u7ec4\u7ec7\u6216\u4e73\u817a\u80bf\u7624\u7ec4\u7ec7\u4e2d\uff0cTreg<\/sub>\u4ece\u672a\u5728\u819c\u4e0a\u6216\u7ec6\u80de\u8d28\u8868\u8fbeCD73\u3002<\/span><\/p>\n

\u4e0e\u5c0f\u9f20\u76f8\u4f3c\uff0c\u5728\u4eba\u7c7b\u4e73\u817a\u80bf\u7624\u4e2d\uff0cTreg<\/sub>\u8868\u8fbe\u9ad8\u6c34\u5e73\u7684CD39\u3002\u6b64\u5916\uff0cTLR-7\u6fc0\u6d3b\u7684pDC\u9009<\/span>\u62e9\u6027\u5730\u8bf1\u5bfcTreg<\/sub>\u4e0aCD39\u6c34\u5e73\u7684\u4e0a\u8c03(\u672a\u53d1\u8868\u7684\u6570\u636e)\u3002<\/p>\n

\u7136\u800c\uff0cCD73\u53ef\u4ee5\u5728\u975eTreg<\/sub> CD4+<\/sup>T\u7ec6\u80de\u4e9a\u7fa4\u4e0a\u89c2\u5bdf\u5230\uff0c\u8fd9\u4e9b\u7ec6\u80de\u80fd\u591f\u5728\u6fc0\u6d3b\u65f6\u589e\u6b96\u5e76\u5206\u6ccc\u9ad8\u6c34\u5e73\u7684IFN-\u03b3\u3002<\/p>\n

\u6211\u4eec\u6700\u8fd1\u7684\u6570\u636e\u663e\u793aCD39+<\/sup>TATreg<\/sub>\u4e0eCD73+<\/sup>CD4+<\/sup>T\u7ec6\u80de\u6548\u5e94\u5668\u534f\u540c\u4ecb\u5bfc\u817a\u82f7\u7684\u4ea7\u751f\u53ca\u5176\u5c40\u90e8\u6291\u5236\u529f\u80fd\uff0c\u8868\u660eCD39\/CD73\u8f74\u662f\u91cd\u8981\u7684Treg<\/sub>\u4ecb\u5bfc\u7684\u6291\u5236\u673a\u5236\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\n

\u9776\u5411DC<\/span>\uff1aTreg<\/sub>\u8868\u9762\u7ec4\u6210\u6027\u8868\u8fbe\u7684CTLA-4\uff0c\u4e0e\u5176\u5728DC\u4e0a\u7684\u914d\u4f53CD80\/CD86\u7684\u76f8\u4e92\u4f5c\u7528\u662fTreg<\/sub>\u4ecb\u5bfc\u5176\u6291\u5236\u529f\u80fd\u7684\u91cd\u8981\u9014\u5f84\u3002<\/p>\n

\u4e8b\u5b9e\u4e0a\uff0cTreg<\/sub>\u5728\u4f53\u5916\u53ef\u4e0b\u8c03\u6216\u6291\u5236DC\u4e0aCD80\u548cCD86\u7684\u4e0a\u8c03\uff0c\u963b\u65ad\u5b83\u4eec\u7684\u5171\u523a\u6fc0\u529f\u80fd\u548c\u968f\u540e\u7684T\u7ec6\u80de\u6fc0\u6d3b\u3002Treg<\/sub>\u4e0a\u8868\u8fbe\u7684Lag-3\u53ef\u80fd\u4e5f\u4f1a\u5728Treg<\/sub>\u8bf1\u5bfc\u7684DC\u529f\u80fd\u6291\u5236\u4e2d\u53d1\u6325\u4f5c\u7528\uff0c\u901a\u8fc7\u4e0e\u672a\u6210\u719fDC\u8868\u8fbe\u7684MHC-II\u7c7b\u5206\u5b50\u7ed3\u5408\uff0c\u8bf1\u5bfcITAM\u4ecb\u5bfc\u7684\u6291\u5236\u4fe1\u53f7\uff0c\u963b\u6b62\u5b83\u4eec\u7684\u6210\u719f\uff0c\u635f\u5bb3\u5b83\u4eec\u7684\u529f\u80fd\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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8.3 \u6cbb\u7597\u7b56\u7565<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n

8.3.1 \u57fa\u4e8epDC\/Treg<\/sub>\u76f8\u4e92\u4f5c\u7528\u7684Treg<\/sub>\u4e2d\u548c\u7b56\u7565<\/strong><\/p>\n<\/section>\n

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\u6211\u4eec\u5f00\u53d1\u4e86\u4e00\u4e2a\u4e34\u5e8a\u76f8\u5173\u7684\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\uff0c\u5728\u8be5\u6a21\u578b\u4e2d\uff0c\u751f\u957f\u5728WT\u5bbf\u4e3b\u4e2d\u7684HER2\/neu+<\/sup>NEU-15\u7ec6\u80de\u7cfb\u901a\u8fc7pDC\u548cTreg<\/sub>\u4ecb\u5bfc\u7684\u514d\u75ab\u66ff\u4ee3\u9003\u907f\u514d\u75ab\u76d1\u89c6\uff0c\u8fd9\u4e0e\u6211\u4eec\u5728\u4eba\u7c7b\u4e73\u817a\u764c\u4e2d\u7684\u89c2\u5bdf\u7ed3\u679c\u975e\u5e38\u76f8\u4f3c(Fig.8.6<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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Fig 8.6 <\/span>\u9488\u5bf9pDC\/Treg<\/sub>\u76f8\u4e92\u4f5c\u7528\u7684\u6cbb\u7597\u7b56\u7565\u3002\u57fa\u4e8e\u5bf9PDC\u4ecb\u5bfc\u7684Treg<\/sub>\u6269\u589e\u7684\u89c2\u5bdf\uff0c\u6211\u4eec\u63d0\u51fa\u4e86\u51e0\u79cd\u4e92\u8865\u7684\u65b9\u6cd5\u6765\u91cd\u65b0\u6fc0\u6d3b\u6297\u80bf\u7624\u514d\u75ab\u3002(1)\u901a\u8fc7 TLR-7 \u914d\u4f53\u5bf9 pDC \u8fdb\u884c\u518d\u6fc0\u6d3b\uff0c\u4fc3\u8fdb\u5176\u4ea7\u751fI \u578b IFN \uff0c\u76ee\u524d\u6709\u4e00\u9879\u4e34\u5e8a\u8bd5\u9a8c\u6b63\u5728\u8fdb\u884c\u4e2d\uff1b(2)TGF-\u03b2\u4e2d\u548c\u4ee5\u6062\u590dpDC\u529f\u80fd\uff0c\u51e0\u79cd\u6297TGF-\u03b2\u53d7\u4f53\u6216TGF-\u03b2\u7684\u6297\u4f53\uff0c\u6216TGF-\u03b2\u53d7\u4f53\u6fc0\u9176\u7ed3\u6784\u57df\u6291\u5236\u5242\u76ee\u524d\u4e5f\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff1b(3)\u901a\u8fc7ICOS\/ICOSL\u4e2d\u548c\u6297\u4f53\u963b\u65adICOS\u4ece\u800c\u6291\u5236Treg\u589e\u6b96\uff1b(4)\u4e2d\u548cCCL22\/CCR4\u4ee5\u963b\u65ad\u80bf\u7624\u5185 Treg \u52df\u96c6\uff0c\u4e2d\u548cCCR4\u6216\u5c0f\u5206\u5b50\u6291\u5236\u5242\u76ee\u524d\u6b63\u5728\u4e34\u5e8a\u8bd5\u9a8c\u548c\/\u6216\u5f00\u53d1\u4e2d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.1.1 TApDC\u7684\u91cd\u65b0\u6fc0\u6d3b<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u901a\u8fc7TLR\u6fc0\u52a8\u5242\u6765\u91cd\u65b0\u6fc0\u6d3bTApDC\u5e76\u8bf1\u5bfc\u5176\u4ea7\u751fIFN-I\u7684\u6cbb\u7597\u7b56\u7565\u53ef\u4ee5\u51cf\u5c11Treg<\/sub>\u7684\u6269\u589e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5c3d\u7ba1\u5b83\u4eec\u5bf9\u80bf\u7624\u8fdb\u5c55\u6709\u8d1f\u9762\u5f71\u54cd\uff0c\u4f46 TApDC \u53ef\u4ee5\u901a\u8fc7\u80bf\u7624\u5185\u6ce8\u5c04 TLR-7L \u5728\u4f53\u5185\u91cd\u65b0\u6fc0\u6d3b\uff0c\u4ece\u800c\u4ecb\u5bfc Th1 \u7279\u5f81\u53cd\u5e94\u548c\u968f\u540e\u7684\u80bf\u7624\u6d88\u9664\u3002TLR-7L \u8bf1\u5bfc\u957f\u671f\u4fdd\u62a4\u6027\u8bb0\u5fc6\u53cd\u5e94\uff0c\u7ed3\u679c\u663e\u793a100% \u6cbb\u6108\u7684\u5c0f\u9f20\u53d7\u5230\u4fdd\u62a4\u514d\u53d7\u968f\u540e\u7684\u80bf\u7624\u653b\u51fb\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u4f53\u5185\u8017\u5c3dpDC\u4f1a\u6291\u5236TLR-7L\u7684\u6cbb\u7597\u6d3b\u6027\uff0c\u8868\u660eTApDC\u5728TLR-7L\u4ecb\u5bfc\u7684\u6297\u80bf\u7624\u53cd\u5e94\u4e2d\u8d77\u5173\u952e\u4f5c\u7528\u3002\u91cd\u8981\u7684\u662f\uff0c\u6211\u4eec\u8bc1\u660e\u4e86\u8fd9\u79cd\u6cbb\u7597\u6d3b\u6027\u662f\u7531\u5c40\u90e8\u8bf1\u5bfc\u7684\uff0c\u800c\u4e0d\u662f\u5168\u8eab\u6027\u7684I\u578b\u5e72\u6270\u7d20\u4ecb\u5bfc\u7684\u3002\u8fd9\u8868\u660e\u4e86\u80bf\u7624\u5185TApDC\u91cd\u65b0\u6fc0\u6d3b\u7684\u91cd\u8981\u6027\uff0c\u8fd9\u5c06\u5bfc\u81f4I\u578b\u5e72\u6270\u7d20\u7684\u4ea7\u751f\uff0c\u4ee5\u53ca\u968f\u540e\u7684\u9644\u52a0\u529f\u80fd\uff0c\u5982\u6297\u539f\u4ea4\u53c9\u63d0\u5448\u548cTreg<\/sub>\u4e2d\u548c\u3002<\/p>\n

\u6211\u4eec\u786e\u5b9e\u89c2\u5bdf\u5230I\u578b\u5e72\u6270\u7d20\u4e2d\u548c\u5bfc\u81f4\u4e86\u80bf\u7624\u5185Th1\u4fe1\u53f7\u7684\u6291\u5236\u3002\u5728\u6b64\u80cc\u666f\u4e0b\uff0c\u54aa\u55b9\u83ab\u7279(TLR7L)\u6cbb\u7597\u76ae\u80a4\u764c\u5bfc\u81f4TApDC\u52df\u96c6\u548cIFN-\u03b1\u7684\u4ea7\u751f\uff0c\u8fd9\u4e0e\u5c40\u90e8\u514d\u75ab\u53cd\u5e94\u548c\u80bf\u7624\u7ec6\u80de\u7684\u7834\u574f\u76f8\u5173\u3002\u54aa\u55b9\u83ab\u7279\u7684\u8fd9\u79cd\u6297\u80bf\u7624\u6d3b\u6027\u4f9d\u8d56\u4e8e\u9897\u7c92\u9176B\u548c\/\u6216TRAIL\u4ecb\u5bfc\u7684TLR7\u6fc0\u6d3b\u7684TApDC\u7684\u76f4\u63a5\u80bf\u7624\u6740\u4f24\u6d3b\u6027\uff0c\u4ece\u800c\u5bfc\u81f4\u968f\u540e\u7684\u6297\u539f\u6355\u83b7\u548c\u4ea4\u53c9\u5448\u9012\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u57fa\u4e8e\u6587\u732e\u7ed3\u679c\uff0c\u6b63\u5728\u8fdb\u884c\u7684I\/II\u671f\u4e34\u5e8a\u8bd5\u9a8c\u76ee\u524d\u6b63\u5728\u8bc4\u4f30TLR\u6fc0\u52a8\u5242\u6cbb\u7597\u5404\u79cd\u7c7b\u578b\u764c\u75c7\u7684\u6cbb\u7597\u6f5c\u529b\u3002\u9274\u4e8e\u6211\u4eec\u89c2\u5bdf\u5230TApDC\u5bf9TLR-7L\u6709\u53cd\u5e94\uff0c\u800c\u5bf9CpG ODN(TLR-9L)\u65e0\u53cd\u5e94\uff0cTLR-7\u6fc0\u52a8\u5242\u5bf9\u4eba\u4e73\u817a\u80bf\u7624\u7684\u6cbb\u7597\u6f5c\u529b\u662f\u503c\u5f97\u8003\u8651\u7684\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.1.2 TGF-\u03b2\u4e2d\u548c<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7528\u514d\u75ab\u8367\u5149\u6cd5(IF)\u68c0\u6d4bBDCA2 TApDC\u7ec6\u80de\u6838\u4e2d\u78f7\u9178\u5316\u7684Smad2\u86cb\u767d\u5728BDCA2 TApDC\u7ec6\u80de\u6838\u4e2d\u7684\u8868\u8fbe\u3002\u8fd9\u4e9b\u89c2\u5bdf\u7ed3\u679c\u8868\u660e\uff0cTApDC\u66b4\u9732\u4e8eBT\u73af\u5883\u4e2d\u65f6\u91ca\u653eTGF-\u03b2\uff0c\u5e76\u63d0\u793aSmad\u4fe1\u53f7\u5728TGF-\u03b2\u4ecb\u5bfc\u7684TApDC\u6291\u5236\u4e2d\u53d1\u6325\u91cd\u8981\u4f5c\u7528\uff0c\u5c31\u50cf\u5df2\u7ecf\u5728\u5c0f\u9f20\u8eab\u4e0a\u8bc1\u660e\u4e86\u7684Smad3\u4e00\u6837\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6211\u4eec\u7684\u7814\u7a76\u786e\u5b9aTGF-\u03b2\u662f\u6062\u590dIFN-I\u751f\u6210\u7684\u65b0\u9776\u70b9\u3002\u56e0\u4e3a\uff081\uff09\u9488\u5bf9\u4ebapDC\u7684TLR-9(CpG ODN)\u548cTLR-7(\u54aa\u55b9\u83ab\u7279)\u914d\u4f53\u76ee\u524d\u6b63\u5728\u80bf\u7624\u60a3\u8005\u7684\u514d\u75ab\u523a\u6fc0\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u8fdb\u884c\u8bc4\u4f30\uff1b(2)\u9488\u5bf9TGF-\u03b2\u6216\u5176\u53d7\u4f53\u4fe1\u53f7\u8f6c\u5bfc\u7684\u836f\u7269\u76ee\u524d\u6b63\u5728\u5f00\u53d1\u4e2d\uff0c(3)pDC\u5bf9\u4e8e\u54aa\u55b9\u83ab\u7279\u901a\u8fc7\u4ea7\u751f\u5e72\u6270\u7d20-\u03b1\u548c\u83b7\u5f97\u7ec6\u80de\u6bd2\u7279\u6027\u800c\u4ecb\u5bfc\u7684\u9ed1\u8272\u7d20\u7624\u5c0f\u9f20\u6a21\u578b\u7684\u6297\u80bf\u7624\u53cd\u5e94\u662f\u5fc5\u8981\u7684\u3002<\/p>\n

\u6211\u4eec\u7684\u7ed3\u679c\u8868\u660e\uff0c\u4f7f\u7528TGF-\u03b2\u62ee\u6297\u5242\u7ed3\u5408TLR7\/9\u6fc0\u6d3b\u6765\u6062\u590dTApDC\u4ea7\u751f\u7684\u5e72\u6270\u7d20-I\u662f\u4e00\u79cd\u6709\u524d\u666f\u7684\u5c40\u90e8BT\u6cbb\u7597\u65b0\u7b56\u7565\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6b64\u5916\uff0c\u7531\u4e8eTGF-\u03b2\u4e5f\u662f\u63a8\u52a8FoxP3+<\/sup>iTreg<\/sub>\u7531\u5916\u5468\u539f\u59cbCD4+<\/sup>T\u7ec6\u80de\u53d1\u5c55\u5206\u5316\u800c\u6765\u7684\u56e0\u7d20\u4e4b\u4e00\uff0c\u90a3\u4e48\u9776\u5411TGF-\u03b2\u901a\u8def\u4e5f\u5c06\u6709\u52a9\u4e8e\u51cf\u5c11Treg<\/sub>\u7684\u4ea7\u751f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.1.3 Treg<\/sub>\u4e0a\u7684ICOS\u4e2d\u548c<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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ICOS\u662fCD28\u5206\u5b50\u8d85\u5bb6\u65cf\u7684\u6210\u5458\uff0c\u5305\u62ecCTLA-4\u3001PD-1\u6216BTLA\uff0c\u5b83\u4eec\u90fd\u5728\u514d\u75ab\u8c03\u8282\u4e2d\u53d1\u6325\u5173\u952e\u4f5c\u7528\u3002\u57fa\u4e8e\u6211\u4eec\u7684\u89c2\u5bdf\u663e\u793aBT\u548c\u6ee4\u6ce1\u6027\u6dcb\u5df4\u7624\u4e2d\u901a\u8fc7ICOS\/ICOS-L\u76f8\u4e92\u4f5c\u7528\u6269\u589eTreg<\/sub>\uff0c\u5e76\u5728\u5375\u5de2\u80bf\u7624\u4e2d\u5f97\u5230\u8bc1\u5b9e\uff0c\u6211\u4eec\u6b63\u5728\u5c06ICOS\u4f5c\u4e3a\u4e2d\u548cTreg<\/sub>\u7684\u6cbb\u7597\u9776\u70b9\u3002\u7136\u800c\uff0c\u5df2\u6709\u7814\u7a76\u8868\u660e\uff0c\u6297CTLA-4\u62ee\u6297\u5242\u6297\u4f53\u7684\u67d0\u4e9b\u4f5c\u7528\u76f4\u63a5\u5f52\u56e0\u4e8eICOS-ICOS-L\u76f8\u4e92\u4f5c\u7528\u7684\u5e72\u6270\u3002<\/p>\n

\u6b64\u5916\uff0cICOS\u8fd8\u8868\u8fbe\u5728\u5176\u4ed6T\u7ec6\u80de\u4e9a\u7fa4\u4e0a\uff0c\u5982TFH\u7ec6\u80de\uff0c\u8fd9\u8868\u660eICOS\u5728\u5b83\u4eec\u7684\u751f\u7269\u5b66\u4e2d\u8d77\u7740\u6838\u5fc3\u4f5c\u7528\u3002Tfh \u7ec6\u80de\u901a\u8fc7\u5728 B \u7ec6\u80de\u6ee4\u6ce1\u5185\u4e3a\u751f\u53d1\u4e2d\u5fc3 B \u7ec6\u80de\u63d0\u4f9b\u5b58\u6d3b\u548c\u5206\u5316\u4fe1\u53f7\uff0c\u6784\u6210\u4e13\u95e8\u8c03\u8282\u4f53\u6db2\u514d\u75ab\u7684\u8f85\u52a9 T \u7ec6\u80de\u4e9a\u7fa4\u3002ICOS\u5728Treg<\/sub>\u548cTfh\u751f\u7269\u5b66\u548c\u75c5\u7406\u751f\u7406\u5b66\u4e2d\u7684\u91cd\u8981\u6027\u9700\u8981\u8fdb\u4e00\u6b65\u63a2\u8ba8\uff0c\u4ee5\u4fbf\u8003\u8651\u5c06ICOS\u4f5c\u4e3a\u4f7f\u7528\u4e2d\u548c\u6297\u4f53\u8fdb\u884c\u514d\u75ab\u6cbb\u7597\u7684\u6f5c\u5728\u9776\u70b9\u3002<\/p>\n

\u6b64\u5916\uff0c\u4e0d\u540c\u7684\u6297ICOS\u6fc0\u52a8\u5242\u5355\u6297(JTX2011(#nct-02904226)\uff0cGSK-3359609(#NXT-02723955))\u76ee\u524d\u6b63\u5728\u665a\u671f\u5b9e\u4f53\u80bf\u7624\u7684I-IIa\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u8fdb\u884c\u8bc4\u4f30\uff0c\u5355\u72ec\u6216\u4e0e\u6297PD-1\u8054\u5408\u6cbb\u7597\uff0c\u4ee5\u91cd\u65b0\u6fc0\u6d3b\u6548\u5e94T\u7ec6\u80de\u53cd\u5e94\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.1.4 CD39\/CD73\u8f74<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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CD73 \u4e0e CD39 \u534f\u540c\u4fc3\u4f7f ATP \u8f6c\u53d8\u4e3a Ado\u3002\u51e0\u4e2a\u56e2\u961f\u5df2\u7ecf\u4f7f\u7528\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u63ed\u793a\u4e86 Ado\/CD73 \u5728\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab\u548c\u4fc3\u8fdb\u80bf\u7624\u53d1\u5c55\u4e2d\u7684\u5173\u952e\u4f5c\u7528 \u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7279\u522b\u662f\u901a\u8fc7\u4e09\u79cd\u4e0d\u540c\u7684\u6280\u672f\u6291\u5236CD73\uff1a(1)shRNAs\uff0c(2)\u5c0f\u5206\u5b50\u5316\u5b66\u6291\u5236\u5242(APCP)\uff0c\u6216(3)\u6297CD73\u5355\u6297(Ty-23)\u901a\u8fc7\u8bf1\u5bfc\u9002\u5e94\u6027\u514d\u75ab\u53cd\u5e94\u800c\u963b\u65ad\u4e73\u817a(T-3)\u548c\u5375\u5de2(ID8)\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u7684\u751f\u957f\u3002\u53cd\u5e94\u5305\u62ec\u63d0\u9ad8\u80bf\u7624\u7279\u5f02\u6027T\u7ec6\u80de\u514d\u75ab\u529b\uff0c\u6539\u5584\u6297\u80bf\u7624T\u7ec6\u80de\u5411\u80bf\u7624\u5fae\u73af\u5883\u7684\u8fd0\u8f93\u3002<\/p>\n

\u5728\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u4e2d\u4e5f\u8bc1\u660e\u4e86Treg<\/sub>\u4ecb\u5bfc\u7684\u90e8\u5206\u514d\u75ab\u6291\u5236\u529f\u80fd\u4f9d\u8d56\u4e8eCD73\u9176\u6d3b\u6027\u3002\u5728\u8fd9\u4e00\u70b9\u4e0a\u76f8\u4e00\u81f4\u7684\u662f\uff0cCD73\u7f3a\u9677\u7684Treg<\/sub>\u5728\u5375\u5de2\u764c\u548c\u6dcb\u5df4\u7624\u7684\u5c0f\u9f20\u6a21\u578b\u4e2d\u8f83\u5c11\u80fd\u591f\u963b\u788d\u80bf\u7624\u7279\u5f02\u6027\u514d\u75ab\u548c\u4fc3\u8fdb\u80bf\u7624\u751f\u957f\u3002<\/p>\n

\u6b64\u5916\uff0c\u817a\u82f7\u901a\u8fc7A2A\u53d7\u4f53\u80fd\u591f\u6709\u6548\u5730\u6291\u5236\u5185\u6e90\u6027\u80bf\u7624\u514d\u75ab\u76d1\u89c6\uff0cA2A\u53d7\u4f53\u7f3a\u9677\u5c0f\u9f20\u81ea\u53d1\u7684\u6297\u80bf\u7624T\u7ec6\u80de\u53cd\u5e94\u80fd\u591f\u8bf1\u5bfcT\u7ec6\u80de\u4f9d\u8d56\u6027\u7684\u80bf\u7624\u6392\u65a5\u53cd\u5e94\u3002<\/p>\n

\u6700\u540e\uff0c\u7ed3\u679c\u8fd8\u663e\u793aCD73\u7684\u7ed3\u6784\u6027\u4e2d\u548c(\u5728CD73 APCP\u5c0f\u9f20\u4e2d)\u6216\u77ac\u65f6\u4e2d\u548c(shRNA\uff0c\u6297\u4f53\uff0cAPCP)\u4e0e\u4efb\u4f55\u660e\u663e\u7684\u514d\u75ab\u75be\u75c5\u65e0\u5173\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u603b\u4e4b\uff0c\u8fd9\u4e9b\u7814\u7a76\u8868\u660e\uff0c\u5e72\u6270CD39\/CD73\/ADAR\u662f\u9006\u8f6cTreg<\/sub>\u4ecb\u5bfc\u7684\u6291\u5236\u7684\u4e00\u79cd\u6f5c\u5728\u7b56\u7565\u3002\u5728\u8fd9\u65b9\u9762\uff0c\u4e24\u5bb6\u516c\u53f8(BMS\uff0cMedImmune)\u76ee\u524d\u6b63\u5728\u8fdb\u884c\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u7528\u6297hCD73 mAb (BMS-986179 #NCT02754141, MEDI-9447# NCT02503774)\u4e0e\u6297PD-1\u6297\u4f53\u8054\u5408\u8fdb\u884c\u6cbb\u7597\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.2 \u57fa\u4e8eTreg<\/sub>\u9776\u5411\/\u8017\u5c3d\u7684\u5176\u4ed6\u7b56\u7565<\/strong><\/p>\n<\/section>\n

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8.3.2.1 \u963b\u65adTreg<\/sub>\u7ec6\u80de\u7684\u8bf1\u5bfc\u548c\u52df\u96c6<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6211\u4eec\u7684\u7814\u7a76\u8868\u660e\uff0cCCL22\u4ecb\u5bfcTreg<\/sub>\u5411\u4eba\u5375\u5de2\u548c\u4e73\u817a\u80bf\u7624\u7684\u8fc1\u79fb\uff0c\u5728\u514d\u75ab\u7f3a\u9677\u7684\u5c0f\u9f20\u5f02\u79cd\u79fb\u690d\u6a21\u578b\u4e2d\uff0c\u963b\u65adCCL22\u663e\u8457\u51cf\u5c11\u4e86Treg<\/sub>\u5411\u5375\u5de2\u80bf\u7624\u7684\u8fc1\u79fb\uff0c\u5bfc\u81f4\u5728\u6297\u80bf\u7624\u6548\u5e94T\u7ec6\u80de\u5b58\u5728\u7684\u60c5\u51b5\u4e0b\u53d1\u751f\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002<\/p>\n

\u8d8b\u5316\u56e0\u5b50\u53d7\u4f53\u5c0f\u5206\u5b50\u62ee\u6297\u5242(AF-399)\u6216\u5355\u6297(Mogalizumab)\u80fd\u591f\u5728\u4f53\u5916\u963b\u65adCCL22\u4ecb\u5bfc\u7684\u4ebaTreg<\/sub>\u548cTh2\u7ec6\u80de\u7684\u52df\u96c6\uff0c\u5e76\u5df2\u8fdb\u5165I\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u7528\u4e8e\u665a\u671f\u5b9e\u4f53\u764c\u60a3\u8005(\u80ba\u764c\u3001\u80c3\u764c\u3001\u98df\u7ba1\u764c\u548c\u80be\u764c)\u5355\u72ec\u6216\u8054\u5408\u6297PD-1(#NCT02946671)\u7684\u6cbb\u7597\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.2.2 Treg<\/sub>\u8017\u5c3d<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5316\u7597\u65b9\u6848\uff1a\u8282\u5f8b\u5242\u91cf\u7684\u73af\u78f7\u9170\u80fa\u6216\u7d2b\u6749\u9187\u53ef\u9009\u62e9\u6027\u964d\u4f4eTreg<\/sub>\u6570\u91cf\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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CD25\u8868\u8fbe\u7ec6\u80de\u7684\u8017\u7aed\uff1aCD25\u4ecd\u7136\u662fTreg<\/sub>\u8017\u7aed\u7b56\u7565\u7684\u4e3b\u8981\u9776\u70b9\u3002\u5728\u5c0f\u9f20\u6a21\u578b\u4e2d\uff0c\u6297 CD25 mAb (PC61) \u7684\u6d88\u8017\u6027\u7ed9\u836f\u53ef\u5f15\u8d77\u5916\u5468\u6dcb\u5df4\u7ec4\u7ec7\u4e2d\u7684 Treg \u5f3a\u70c8\u51cf\u5c11\u5e76\u8bf1\u5bfc\u5df2\u5f62\u6210\u7684\u80bf\u7624\u7684\u6d88\u9000\u3002<\/p>\n

\u51e0\u79cd\u9488\u5bf9CD25\u7684\u836f\u7269\u6b63\u5728\u8fdb\u884c\u4e34\u5e8a\u8bd5\u9a8c\uff1a<\/p>\n

(1) \u5fb7\u5c3c\u7f57\u91d1\u5730\u585e\u7c73\u677e(Denileukin Diftitox)(Ontak\u00ae<\/sup>\uff0cDAB389IL-2)\u662f\u4e00\u79cd\u5c06\u767d\u5589\u6bd2\u7d20\u6d3b\u6027\u533a\u57df\u4e0e\u4ebaIL-2\u878d\u5408\u7684\u91cd\u7ec4\u86cb\u767d\uff1b<\/p>\n

(2)Daclizumab(zentex\u00ae<\/sup>)\u548c\u5df4\u5229\u6614\u5355\u6297(Simect\u00ae<\/sup>)\u662f\u6297\u4ebaCD25\u5355\u6297\u3002<\/p>\n

\u7136\u800c\uff0c\u7531\u4e8eCD25\u7684\u975e\u7279\u5f02\u6027\u8868\u8fbe\uff0c\u8fd9\u79cd\u7b56\u7565\u7684\u4e3b\u8981\u98ce\u9669\u662f\u53ef\u80fd\u4f1a\u6e05\u9664\u80bf\u7624\u5185\u5b58\u5728\u7684\u6d3b\u5316T\u7ec6\u80de\uff0c\u8fd9\u4e9bT\u7ec6\u80de\u6709\u52a9\u4e8eT\u7ec6\u80de\u6297\u80bf\u7624\u514d\u75ab\u7684\u542f\u52a8\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6297CTLA-4\u8017\u7aed\u6027\u6297\u4f53\uff1a\u5176\u4ed6Treg<\/sub>\u53d7\u4f53\u4e5f\u53ef\u4ee5\u5b9e\u73b0Treg<\/sub>\u9776\u5411\uff0c\u5176\u4e2d\uff0c\u6297CTLA-4\u5355\u6297\u7684\u7814\u7a76\u8f83\u591a\u3002BMS(MDX-100\uff1a\u6613\u666e\u5229\u59c6\u739b\uff08\u836f\u540d\uff09\u00ae<\/sup>\/yervov\u00ae<\/sup>)\u548c\u8f89\u745e\/\u963f\u65af\u5229\u5eb7(CP675206\uff1atremlimumab\u00ae<\/sup>)\u5f00\u53d1\u7684\u4e24\u79cd\u5b8c\u5168\u4eba\u6e90\u5316\u5355\u6297\u5df2\u7ecf\u5728\u4e0d\u540c\u80bf\u7624\u7c7b\u578b\u7684\u764c\u75c7\u60a3\u8005\u4e2d\u8fdb\u884c\u4e86\u4e34\u5e8a\u8bd5\u9a8c\u3002\u57fa\u4e8e\u5c0f\u9f20\u7814\u7a76\uff0c\u63d0\u51faIgG1\u540c\u578b(ADCC\u6d3b\u6027)\u7684\u6613\u666e\u5229\u59c6\u739b\uff08\u836f\u540d\uff09\u7684\u90e8\u5206\u6cbb\u7597\u6d3b\u6027\u662f\u901a\u8fc7\u8017\u5c3d\u7ec6\u80de\u8868\u9762CTLA4\u6613\u4f4d\u6fc0\u6d3b\u7684Treg<\/sub>\u3002\u8fd9\u5df2\u7ecf\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\u7684\u4f53\u5916\u5b9e\u9a8c\u5f97\u5230\u8bc1\u5b9e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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8.3.2.3 \u963b\u65adTreg<\/sub>\u529f\u80fd<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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TNFR\u5bb6\u65cf\uff1aTNFR\u5bb6\u65cf\u6709\u51e0\u4e2a\u6210\u5458(OX40\u3001GITR\u3001CD137\u7b49)\u3002\u76ee\u524d\u5c1a\u4e0d\u6e05\u695a\u5982\u4f55\u5728\u4e0d\u635f\u5bb3T\u6548\u5e94\u529f\u80fd\u7684\u60c5\u51b5\u4e0b\u963b\u65adTreg<\/sub>\u529f\u80fd\u3002\u4e0e\u6297CTLA-4\u7c7b\u4f3c\uff0cADCC\u6d3b\u6027\u6fc0\u52a8\u5242\u6297GITR\u5355\u6297\u53ef\u8bf1\u5bfcTreg<\/sub>\u8017\u7aed\uff0c\u540c\u65f6\u901a\u8fc7\u5176\u6fc0\u52a8\u5242\u6d3b\u6027\u8bf1\u5bfcT\u6548\u5e94\u5668\u7684\u6fc0\u6d3b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u901a\u8fc7TLR\u6fc0\u52a8\u5242\u963b\u65adTreg<\/sub>\u6291\u5236\u529f\u80fd\uff1aTLR-2\u4fe1\u53f7(PAM2CSK4\u3001PAM3CSK4\u3001FSL-1)\u5728\u4f53\u5916\u548c\u4f53\u5185\u80bf\u7624\u6a21\u578b\u4e2d\u53ef\u964d\u4f4eTreg<\/sub>\u6291\u5236\u529f\u80fd\u3002Treg<\/sub>\u4ecb\u5bfc\u7684\u6291\u5236\u5728\u4f53\u5916\u53ef\u4ee5\u88abTLR-8\u884d\u751f\u4fe1\u53f7\u6291\u5236\uff0c\u800c\u7528CpG(TLR-9\u6fc0\u52a8\u5242)\u5728\u4f53\u5185\u6cbb\u7597\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4f1a\u5bfc\u81f4Treg<\/sub>\u7684\u6570\u91cf\u964d\u4f4e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6211\u4eec\u7684\u5de5\u4f5c\u5f3a\u8c03\u4e86Treg<\/sub>\/pDC\u76f8\u4e92\u4f5c\u7528\u5728\u4e73\u817a\u548c\u5375\u5de2\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684\u91cd\u8981\u6027\u3002\u80bf\u7624\u7ec6\u80de\u5728NK\u548c\u5de8\u566c\u7ec6\u80de\u6d3b\u5316\u540e\u5206\u6ccc\u708e\u6027\u7ec6\u80de\u56e0\u5b50\uff0c\u901a\u8fc7CCR4\u548cCCL22\u52df\u96c6Treg<\/sub>\u3002\u62db\u52df\u7684 TATreg \u968f\u540e\u88ab TApDC \u6269\u589e\uff0c\u7531\u4e8e TGF-\u03b2\u66b4\u9732\u548c smad2 \u5728\u80bf\u7624\u73af\u5883\u4e2d\u78f7\u9178\u5316\uff0c\u5b83\u4eec\u4ea7\u751f IFN \u7684\u80fd\u529b\u6709\u7f3a\u9677\u3002\u6269\u589e\u7684Treg<\/sub>\u8868\u8fbe\u4e0a\u8c03\u7684CD39\uff0cCD73\u5728\u6548\u5e94\u5668\u7ec6\u80de\u4e0a\u7684\u8868\u8fbe\u5c06\u901a\u8fc7\u817a\u82f7\u7684\u4ea7\u751f\u4ecb\u5bfc\u514d\u75ab\u6291\u5236\u3002\u8fd9\u79cd\u6291\u5236\u901a\u8def\u53ef\u80fd\u5728\u5bfc\u81f4\u80bf\u7624\u7ec6\u80de\u6b7b\u4ea1\u548cATP\u91ca\u653e\u7684\u5316\u7597\u8fc7\u7a0b\u4e2d\u7279\u522b\u76f8\u5173\u3002<\/p>\n

\u8fd9\u79cdpDC\/Treg<\/sub>\u76f8\u4e92\u4f5c\u7528\u7684\u9014\u5f84\u786e\u5b9a\u4e86\u51e0\u4e2a\u6062\u590d\u6297\u80bf\u7624\u514d\u75ab\u7684\u6f5c\u5728\u9776\u70b9\uff1a(1)mAb\u4e2d\u548cCCL22\/CCR4\u4ee5\u963b\u65adTreg<\/sub>\u5728\u80bf\u7624\u5185\u7684\u91cd\u65b0\u52df\u96c6\uff1b(2)pDC\u901a\u8fc7TLR-7\u914d\u4f53\u91cd\u65b0\u6fc0\u6d3b\u4ee5\u4ea7\u751fI\u578b\u5e72\u6270\u7d20\uff1b(3)TGF-\u03b2\u4e2d\u548c\u4ee5\u6062\u590dpDC\u529f\u80fd\uff1b\u4ee5\u53ca(4)\u901a\u8fc7ICOS\/ICOSL\u4e2d\u548cmAb\u4e2d\u548cICOS\u4ee5\u963b\u65adTreg<\/sub>\u589e\u6b96\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><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n


<\/p>\n

\u2014 THE  END \u2014<\/span><\/p>\n


<\/p>\n

\u6765\u6e90 | Oncoimmunology: A Practical Guide <\/span><\/section>\n
for Cancer Immunotherapy<\/span><\/section>\n
\u4f5c\u8005 | <\/span>N. Bendriss-Vermare, N. Gourdin, N. Vey, J. Faget,<\/span><\/section>\n

V. Sisirak, I. Labidi-Galy, I. Le Mercier, N. Goutagny,<\/span><\/p>\n

I. Puisieux, C. M\u00e9n\u00e9trier-Caux, and C. Caux<\/span><\/p>\n

\u7ffb\u8bd1 |   \u9648\u8389\u8679 \u949f\u96ea\u83b9 \u9648\u6653\u610f<\/span><\/section>\n
\u7f16\u8f91\u6392\u7248 | \u9648\u8389\u8679<\/span><\/span><\/section>\n
\u521d\u5ba1 | \u5ed6\u5a9b \u4efb\u632f\u9633<\/span><\/section>\n
\u7ec8\u5ba1 | \u738b\u5764 \u8096\u5efa\u52c7<\/span><\/section>\n
\uff08\u8f6c\u8f7d\u8bf7\u4fdd\u7559\u6b64\u90e8\u5206\u5185\u5bb9\uff09<\/span><\/strong><\/section>\n

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\u2589  \u5f80\u671f\u6587\u7ae0<\/strong><\/strong><\/p>\n

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\u7f51\u7ad9\u81ea\u5e26\u68c0\u7d22\u529f\u80fd\uff0c\u53ef\u4ee5\u6839\u636e\u5173\u952e\u8bcd\u8fdb\u884c\u68c0\u7d22\uff0c\u5e76\u4e14\u53ef\u4ee5\u6839\u636e\u65e5\u671f\u53ca\u5185\u5bb9\u5206\u7c7b\u8fdb\u884c\u67e5\u770b ,\u5927\u5bb6\u53ef\u4ee5\u6536\u85cf\u65b9\u4fbf\u5728\u7535\u8111\u4e0a\u67e5\u770b\u3002<\/p>\n

\u7f51\u5740\u662f\uff1aoncolab.cn<\/span><\/strong><\/p>\n<\/section>\n

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\u8d5e\u4e0e\u5728\u770b <\/span><\/section>\n
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