{"id":2615,"date":"2022-06-28T22:46:46","date_gmt":"2022-06-28T14:46:46","guid":{"rendered":"http:\/\/oncolab.cn\/index.php\/2022\/06\/28\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac10%e7%ab%a0%ef%bc%9a%e9%aa%a8%e9%ab%93%e6%ba%90%e6%80%a7%e6%8a%91%e5%88%b6%e6%80%a7%e7%bb%86%e8%83%9emdscs%e7%9a%84%e7%94%9f%e7%89%a9%e5%ad%a6-2\/"},"modified":"2022-06-28T22:46:46","modified_gmt":"2022-06-28T14:46:46","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac10%e7%ab%a0%ef%bc%9a%e9%aa%a8%e9%ab%93%e6%ba%90%e6%80%a7%e6%8a%91%e5%88%b6%e6%80%a7%e7%bb%86%e8%83%9emdscs%e7%9a%84%e7%94%9f%e7%89%a9%e5%ad%a6-2","status":"publish","type":"post","link":"http:\/\/oncolab.cn\/index.php\/2022\/06\/28\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac10%e7%ab%a0%ef%bc%9a%e9%aa%a8%e9%ab%93%e6%ba%90%e6%80%a7%e6%8a%91%e5%88%b6%e6%80%a7%e7%bb%86%e8%83%9emdscs%e7%9a%84%e7%94%9f%e7%89%a9%e5%ad%a6-2\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c10\u7ae0\uff1a\u9aa8\u9ad3\u6e90\u6027\u6291\u5236\u6027\u7ec6\u80de(MDSCs)\u7684\u751f\u7269\u5b66\u7279\u6027\uff08\u4e0b\uff09"},"content":{"rendered":"
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10.4 MDSCs\u7684\u7d2f\u79ef\u53ca\u529f\u80fd\u7684\u8c03\u63a7\u673a\u5236<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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MDSC<\/strong>\u7814\u7a76\u9886\u57df\u7684\u4e00\u4e2a\u4e3b\u8981\u95ee\u9898\u662f\u5b83\u4eec\u7684\u6269\u589e\u3001\u79ef\u7d2f\u548c\u6fc0\u6d3b<\/strong>\u662f\u5982\u4f55\u8c03\u8282\u7684\uff1f<\/p>\n

\u51e0\u5e74\u524d\uff0c\u6211\u4eec\u63d0\u51fa\u4e86\u4e00\u4e2a\u53cc\u4fe1\u53f7\u6a21\u578b<\/strong>\uff0c\u8be5\u6a21\u578b\u63cf\u8ff0\u4e86MDSC\u7684\u79ef\u7d2f\u9700\u8981\u4e24\u79cd\u4e0d\u540c\u7c7b\u578b\u7684\u4fe1\u53f7\u3002\u8be5\u6a21\u578b\u5206\u4e3a\u4e24\u4e2a\u9636\u6bb5\uff1a(1)\u6269\u589e\u9636\u6bb5<\/strong>\uff0c\u4e0e\u5176\u7ec8\u672b\u5206\u5316\u6291\u5236\u76f8\u5173\uff1b(2)\u6fc0\u6d3b\u9636\u6bb5<\/strong>\uff0c\u8d1f\u8d23\u5c06\u672a\u6210\u719f\u7684\u9ad3\u6837\u7ec6\u80de\u8f6c\u5316\u4e3a\u514d\u75ab\u6291\u5236\u7684MDSCs\u3002<\/p>\n

\u6211\u4eec\u8ba4\u4e3a\uff0c\u8fd9\u4e24\u4e2a\u9636\u6bb5\u90e8\u5206\u91cd\u53e0\uff0c\u4f46\u53d7\u4e0d\u540c\u7684\u8f6c\u5f55\u56e0\u5b50<\/strong>\u548c\u4e2d\u95f4\u4ea7\u7269<\/strong>\u63a7\u5236(<\/span>Fig10.3<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig.10.3 <\/span>\u80bf\u7624\u76f8\u5173\u56e0\u5b50\u548c\u5206\u5b50\u901a\u8def\u8c03\u8282\u80bf\u7624\u4e2dMDSC\u7684\u6269\u589e\u548c\u529f\u80fd\u3002\u80bf\u7624\u5fae\u73af\u5883\u4ea7\u751f\u4e86\u5927\u91cf\u7684\u7ec6\u80de\u56e0\u5b50\u548c\u514d\u75ab\u6291\u5236\u4ecb\u8d28\uff0c\u4fe1\u53f71\u548c2\u5206\u522b\u8c03\u8282MDSC\u7684\u6269\u589e\u548c\u514d\u75ab\u6291\u5236\u6d3b\u6027\u3002MDSC\u66b4\u9732\u5728\u80bf\u7624\u5206\u6ccc\u7684\u751f\u957f\u56e0\u5b50(\u4fe1\u53f71)\u548c\u5176\u4ed6\u4ecb\u8d28\u4e2d\uff0c\u8c03\u8282M-MDSC\u6216PMN-MDSC\u6269\u589e\u548c\u805a\u96c6\u8fc7\u7a0b\u4e2d\u6d89\u53ca\u7684\u51e0\u4e2a\u4fe1\u53f7\u901a\u8def\uff0c\u7279\u522b\u662fSTAT3\u3002\u7136\u800c\uff0c\u5bf9\u4e8e\u672a\u6210\u719f\u7684\u9ad3\u6837\u7ec6\u80de\u83b7\u5f97\u514d\u75ab\u6291\u5236\u6d3b\u6027\uff0c\u9700\u8981\u4fe1\u53f72\u6765\u540c\u65f6\u4ea7\u751fM-MDSCs\u548cPMN-MDSCs\u3002\u8fd9\u4e9b\u4fe1\u53f7\u901a\u8def\u5bf9\u4e8ePMN-MDSCs\u548cM-MDSCs(NF-\u03baB\u3001STAT3\u3001STAT6\u3001ER\u5e94\u6fc0\u53cd\u5e94)\u90fd\u5f88\u91cd\u8981\uff0c\u6216\u8005\u53ef\u80fd\u5728MDSC\u4e9a\u7fa4(STATT1)\u4e2d\u5177\u6709\u76f8\u53cd\u7684\u4f5c\u7528\u3002COX-2\u5bf9M-MDSCs\u66f4\u5177\u6709\u7279\u5f02\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7b2c\u4e00\u9636\u6bb5<\/strong>\u4e3b\u8981\u7531\u80bf\u7624\u884d\u751f\u751f\u957f\u56e0\u5b50\u4ee5\u53caSTAT3\u3001IRF8\u3001C\/EBP\u03b2\u3001RB1\u3001NOTCH\u3001\u817a\u82f7\u53d7\u4f53A2B\u548cNLRP3\u9a71\u52a8\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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STAT3<\/strong><\/p>\n

MDSCs\u4e2d\u4fe1\u53f7\u8f6c\u5bfc\u548c\u8f6c\u5f55\u6fc0\u6d3b\u56e0\u5b503(STAT3<\/strong>)\u7684\u6fc0\u6d3b\u9700\u8981\u9ad3\u7cfb\u7279\u5f02\u6027\u751f\u957f\u56e0\u5b50<\/strong>\uff0c\u5982GM-CSF\u3001G-CSF\u3001M-CSD\u3001IL-6\u3001VEGF\u548c\u5176\u4ed6\u51e0\u79cd\u56e0\u5b50\u3002<\/p>\n

STAT3\u5728MDSCs\u7684\u8c03\u63a7\u4e2d\u8d77\u91cd\u8981\u4f5c\u7528\u3002\u4f8b\u5982\uff0c\u7528\u4e0d\u540c\u7684STAT3\u6291\u5236<\/strong>\u5242\u6cbb\u7597\u7684\u8377\u7624\u5c0f\u9f20\u8868\u73b0\u4e3aMDSC\u79ef\u805a\u51cf\u5c11<\/strong>\u3002<\/p>\n

\u6709\u8da3\u7684\u662f\uff0cSTAT3\u4e0d\u4ec5\u53c2\u4e0eMDSCs\u7684\u6269\u589e\uff0c\u8fd8\u53c2\u4e0e\u5176\u529f\u80fd\u548c\u5206\u5316<\/strong>\uff1b\u4f8b\u5982\uff0cM-MDSCs<\/strong>\u80fd\u591f\u901a\u8fc7STAT3<\/strong>\u7684\u8c03\u8282\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u5206\u5316\u4e3a\u80bf\u7624\u76f8\u5173\u5de8\u566c\u7ec6\u80de(TAMs)<\/strong>\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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IRF8 <\/strong><\/p>\n

\u5e72\u6270\u7d20\u8c03\u8282\u56e0\u5b508(IRF8)\u88ab\u8ba4\u4e3a\u662fMDSC\u5206\u5316\u7684\u8d1f\u8c03\u63a7\u56e0\u5b50<\/strong>\u3002\u6ca1\u6709IRF8\u7684\u60c5\u51b5\u4e0b\uff0cMDSC\u5728\u813e\u810f\u548c\u80bf\u7624\u7ec4\u7ec7\u4e2d\u7684\u79ef\u805a\u589e\u52a0\uff1b\u7136\u800c\uff0c\u5728\u81ea\u53d1\u7684\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u4e2d\uff0cIRF8\u7684\u8fc7\u8868\u8fbe\u4f1a\u5bfc\u81f4MDSCs\u79ef\u805a\u51cf\u5c11\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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C\/EBP\u03b2<\/strong><\/p>\n

CAAT\u589e\u5f3a\u5b50\u7ed3\u5408\u86cb\u767d\u03b2(C\/eBP\u03b2)\u662f\u5176\u5bb6\u65cf\u4e2d\u552f\u4e00\u4e0eMDSC\u6269\u589e\u76f8\u5173<\/strong>\u7684\u6210\u5458\u3002\u7f3a\u4e4f\u9020\u8840\u7ec6\u80de\u7279\u5f02\u6027C\/EBP\u03b2\u7684\u5c0f\u9f20\u7684MDSCs\u6570\u91cf\u8f83\u5c11\uff0c\u5c24\u5176\u662fM-MDSCs\uff0c\u8868\u660e\u5176\u5728MDSCs\u5206\u5316\u4e2d\u8d77\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Rb1 <\/strong><\/p>\n

\u89c6\u7f51\u819c\u6bcd\u7ec6\u80de\u7624\u86cb\u767d1(Rb1)\u4e0e\u5728\u5c0f\u9f20\u548c\u4eba\u7c7b\u4e2d\u53d1\u73b0\u7684MDSCs\u6709\u5173\u3002\u5728\u8377\u7624\u5c0f\u9f20\u4e2d\uff0cRb1\u88ab\u8bc1\u660e\u53ef\u4ee5\u8c03\u8282M-MDSCs\u5411PMN-MDSCs\u5206\u5316<\/strong>\u3002\u9ad8Rb1\u6c34\u5e73<\/strong>\u7684M-MDSCs\u4e3b\u8981\u4ea7\u751f\u5de8\u566c\u7ec6\u80de\u548cDC<\/strong>\uff0c\u800cRb1\u6c34\u5e73\u4f4e<\/strong>\u7684M-MDSCs\u7edd\u5927\u591a\u6570\u5206\u5316\u4e3aPMN-MDSCs<\/strong>\u3002\u6700\u8fd1\uff0c\u5728\u5c0f\u9f20\u4e73\u817a\u764c\u8f6c\u57fa\u56e0\u6a21\u578b\u4e2d\u8bc1\u5b9e\u4e86\u5b58\u5728Rb1lo<\/sup> Ly6G+<\/sup>PMN-MDSC\u7684\u84c4\u79ef\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Notch \u4fe1\u53f7\u901a\u8def<\/strong><\/p>\n

\u53e6\u4e00\u6761\u53c2\u4e0eMDSCs\u805a\u96c6\u548c\u5206\u5316<\/strong>\u7684\u9014\u5f84\u662fNotch\u4fe1\u53f7\u901a\u8def\u3002\u5df2\u6709\u7814\u7a76\u8868\u660e\uff0c\u5728MDSCs\u4e2d\uff0c\u916a\u86cb\u767d\u6fc0\u91762(CKII)<\/strong>\u7684\u6fc0\u6d3b\u4e0b\u8c03\u4e86Notch\u7684\u8868\u8fbe\u3002<\/p>\n

\u56e0\u6b64\uff0c\u7528CKII\u6291\u5236\u5242\u6cbb\u7597\u7684\u8377\u7624\u5c0f\u9f20\u5728Notch\u4fe1\u53f7\u548cDC\u5206\u5316\u65b9\u9762\u8868\u73b0\u51fa\u6539\u5584\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0cNotch\u4fe1\u53f7\u7684\u4e0b\u8c03\u4f7f\u9020\u8840\u5e72\u7ec6\u80de\u5411MDSCs\u5206\u5316\u800c\u4e0d\u662f\u5411DC\u5206\u5316\u3002<\/p>\n

\u6700\u8fd1\uff0c\u7814\u7a76\u8868\u660e\uff0cNotch \u4fe1\u53f7\u7684\u6291\u5236\u589e\u5f3a\u4e86 PMN-MDSCs<\/strong> \u7684\u4ea7\u751f\uff0c\u4f46\u51cf\u5c11\u4e86 M-MDSCs<\/strong> \u7684\u4ea7\u751f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Adenosine Receptor A2B<\/strong><\/p>\n

\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\uff0c\u901a\u8fc7\u4e0eMDSC\u4e0a\u8868\u8fbe\u7684\u817a\u82f7\u53d7\u4f53A2B<\/strong>\u7ed3\u5408\uff0c\u7ec6\u80de\u5916\u817a\u82f7\u6c34\u5e73\u5347\u9ad8\uff0c\u8fd9\u4e0eMDSC\u805a\u96c6\u6709\u5173<\/strong>\u3002<\/p>\n

\u4e0e\u91ce\u751f\u578b\u76f8\u6bd4\uff0c\u7f3a\u4e4fA2B\u7684\u8377\u7624\u5c0f\u9f20\u7684MDSCs\u6570\u91cf\u8f83\u5c11\uff0c\u8fd9\u8868\u660eA2B\u53d7\u4f53\u5728MDSCs\uff0c\u7279\u522b\u662fPMN-MDSCs\u7684\u6269\u589e\u4e2d\u8d77\u5173\u952e\u4f5c\u7528\u3002<\/p>\n

\u8fd9\u4e0e\u6700\u8fd1\u4e00\u9879\u4f7f\u7528A2B\u6fc0\u52a8\u5242\u548c\u62ee\u6297\u5242\u6cbb\u7597\u9ed1\u8272\u7d20\u7624\u6a21\u578b\u7684\u7814\u7a76\u6709\u5173\uff0c\u5728\u8be5\u6a21\u578b\u4e2d\uff0c\u6fc0\u52a8\u5242\u6cbb\u7597\u589e\u52a0\u4e86\u80bf\u7624\u751f\u957f\u548cMDSC\u79ef\u805a\uff0c\u800c\u62ee\u6297\u5242\u6cbb\u7597\u5bfc\u81f4\u80bf\u7624\u8fdb\u5c55\u51cf\u7f13\uff0c\u80bf\u7624\u7ec4\u7ec7\u4e2dMDSC\u6570\u91cf\u51cf\u5c11\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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NLRP3 <\/strong><\/p>\n

NLR3(NLRP3)\u662f\u4e00\u79cd\u4e0e\u708e\u75c7\u5c0f\u4f53\u76f8\u5173\u7684\u7ec6\u80de\u5185\u611f\u53d7\u5668\uff0c\u6fc0\u6d3b\u540e\u53ef\u8bf1\u5bfc\u767d\u7ec6\u80de\u4ecb\u7d20-1(IL-1)\u03b2<\/strong>\u548cIL-18<\/strong>\u7684\u4ea7\u751f\u3002<\/p>\n

\u80bf\u7624\u76f8\u5173\u7684MDSCs\u8868\u8fbeNLRP3\uff0c\u4e0e\u91ce\u751f\u578b\u5c0f\u9f20\u76f8\u6bd4\uff0cNlrp3\u2212\/\u2212<\/sup>\u5c0f\u9f20\u80bf\u7624\u7ec4\u7ec7\u4e2dMDSCs\u7684\u6c34\u5e73\u8f83\u4f4e\uff0c\u8fd9\u8868\u660eNLRP3\u53ef\u80fd\u5728MDSCs\u7684\u6269\u589e\u548c\u79ef\u7d2f\u4e2d\u53d1\u6325\u4f5c\u7528\u3002<\/p>\n

\u7136\u800c\uff0c\u9700\u8981\u66f4\u591a\u7684\u7814\u7a76\u6765\u786e\u5b9aNLRP3\u5728MDSC\u529f\u80fd\u4e2d\u7684\u786e\u5207\u4f5c\u7528\u3002\u663e\u7136\uff0c\u8fd9\u4e9b\u4fe1\u53f7\u901a\u8def\u8c03\u8282MDSC\u7684\u6269\u589e\uff0c\u5e76\u53c2\u4e0e\u963b\u6b62\u6b63\u5e38\u7684\u672a\u6210\u719f\u9ad3\u7cfb\u7ec6\u80de\u5206\u5316<\/strong>\u3002<\/p>\n

\u7136\u800c\uff0c\u8fd9\u4e9b\u56e0\u5b50\u4e2d\u7684\u5927\u591a\u6570\u90fd\u4e0eMDSC\u8c03\u8282\u7684\u7b2c\u4e00\u9636\u6bb5\u6709\u5173\uff0c\u4f46\u8fd9\u4e5f\u5e76\u4e0d\u8db3\u4ee5\u4fc3\u8fdb\u5b83\u4eec\u88ab\u6fc0\u6d3b\u6210\u4e3a\u514d\u75ab\u6291\u5236\u7ec6\u80de(Fig10.3<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u4f5c\u4e3a\u6211\u4eec\u53cc\u4fe1\u53f7\u6a21\u578b\u7684\u4e00\u90e8\u5206\uff0c\u5728MDSCs\u4e2d\u53d1\u73b0\u7684\u6291\u5236\u6d3b\u6027\u7684\u4ea7\u751f\u4e3b\u8981\u662f\u7531\u80bf\u7624\u57fa\u8d28\u4ea7\u751f\u7684\u56e0\u5b50<\/strong>\u4ecb\u5bfc\u7684\uff0c\u5305\u62ec\u4fc3\u708e\u5206\u5b50\uff0c\u5982\u5e72\u6270\u7d20\u03b3\uff0cIL-1\u03b2\uff0cIL-13\uff0cToll\u6837\u53d7\u4f53\u914d\u4f53<\/strong>\u7b49\u3002<\/p>\n

\u8fd9\u4e9b\u5206\u5b50\u4e2d\u7684\u6bcf\u4e00\u4e2a\u90fd\u53c2\u4e0e\u4e86\u591a\u79cd\u4fe1\u53f7\u901a\u8def\u7684\u6fc0\u6d3b\uff0c\u5176\u4e2d\u5305\u62ecNF-\u03baB\u3001STAT1\u3001STAT6\u3001\u524d\u5217\u817a\u7d20E2(PGE2)\u548c\u73af\u6c27\u5408\u9176(COX-2)\u3001\u9ad8\u8fc1\u79fb\u7387\u65cf\u86cb\u767d1(HMGB1)\u548c\u7f3a\u6c27\u8bf1\u5bfc\u56e0\u5b50-1\u03b1(HIF-1\u03b1)<\/strong>\uff0c\u4ed6\u4eec\u90fd\u4e0eMDSCs\u7684\u6291\u5236\u6d3b\u6027\u6709\u5173\u3002<\/p>\n

\u6700\u8fd1\uff0c\u5185\u8d28\u7f51(ER)\u5e94\u6fc0<\/strong>\u9014\u5f84\u88ab\u8ba4\u4e3a\u4e0e\u80bf\u7624\u4e2d\u53d1\u73b0\u7684MDSCs\u7684\u6291\u5236\u6d3b\u6027\u6709\u5173\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

NF-\u03baB<\/strong><\/p>\n

\u5728MDSCs\u4e2d\uff0cNF-\u03baB\u901a\u8def\u7684\u6fc0\u6d3b<\/strong>\u4e3b\u8981\u662f\u7531TLR\u914d\u4f53:IL-1\u03b2\u6216TNF-\u03b1<\/strong>\u4ecb\u5bfc\u7684\uff0cIL-1\u03b2\u6216TNF-\u03b1\u5747\u88ab\u8bc1\u660e\u80fd\u589e\u5f3a\u6291\u5236\u6d3b\u6027<\/strong>\u3002<\/p>\n

TLR\u914d\u4f53\u5728MDSC\u529f\u80fd\u4e2d\u7684\u4f5c\u7528\u5c1a\u4e0d\u6e05\u695a\u3002\u4e00\u4e9b\u7814\u7a76\u8868\u660e\uff0cTLR\u914d\u4f53\u9a71\u52a8MDSCs\u7684\u6291\u5236\u6d3b\u6027\uff0c\u800c\u53e6\u4e00\u4e9b\u7814\u7a76\u8868\u660e\u8fd9\u4e9b\u914d\u4f53\u6291\u5236\u5176\u529f\u80fd\u3002<\/p>\n

\u5728\u708e\u75c7\u548c\u764c\u75c7\u8fc7\u7a0b\u4e2d\uff0c\u80bf\u7624\u7ec6\u80de\u4ea7\u751f\u7684IL-1\u03b2<\/strong>\u901a\u8fc7NF-\u03baB\u9014\u5f84\u6fc0\u6d3bMDSCs<\/strong>\uff0c\u5bfc\u81f4PNT\u7684\u4ea7\u751f<\/strong>\u589e\u52a0\u3002\u53e6\u4e00\u4e2a\u4f17\u6240\u5468\u77e5\u7684NF-\u03baB\u9014\u5f84\u7684\u6fc0\u6d3b\u5242\u662f\u80bf\u7624\u574f\u6b7b\u56e0\u5b50-\u03b1(TNF-\u03b1)<\/strong>\uff0c\u5b83\u4e0eMDSCs\u7684\u6210\u719f\u548c\u529f\u80fd\u6709\u5173\u3002<\/p>\n

\u7ed3\u679c\u8868\u660e\uff0c\u8de8\u819c\u578bTNF-\u03b1<\/strong>\u53ef\u901a\u8fc7\u5176\u53d7\u4f53\u589e\u5f3aMDSCs\u7684\u6291\u5236\u6d3b\u6027\uff0c\u5e76\u4ee5NF-\u03baB\u4f9d\u8d56\u7684\u65b9\u5f0f\u8c03\u8282iNOS\u7684\u8868\u8fbe\u3002<\/p>\n

\u4e00\u9879\u4f7f\u7528\u708e\u75c7\u5c0f\u9f20\u6a21\u578b\u7684\u7814\u7a76\u8868\u660e\uff0cTNF-\u03b1\u7684\u4f5c\u7528\u4ec5\u9650\u4e8eM-MDSCs<\/strong>\u3002\u6b64\u5916\uff0c NF-\u03baB\u901a\u8fc7TNF-\u03b1\u53d7\u4f53\u6fc0\u6d3b\u53ef\u4ee5\u4fc3\u8fdbMDSCs\u7684\u5b58\u6d3b\u3002\u76ee\u524d\uff0cNF-\u03baB\u53ef\u4ee5\u53c2\u4e0e\u9aa8\u9ad3\u95f4\u5145\u8d28\u5e72\u7ec6\u80de\u7684\u6269\u589e\uff0c\u4f46\u5b83\u7684\u4e3b\u8981\u4f5c\u7528\u662f\u53d1\u51fa\u4fe1\u53f7\u6fc0\u6d3b\u8fd9\u4e9b\u7ec6\u80de\uff0c\u4ece\u800c\u83b7\u5f97\u6291\u5236\u8868\u578b\uff0c\u7279\u522b\u662f\u5728M-MDSCs\u4e2d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

STAT1 <\/strong><\/p>\n

\u4e00\u4e9b\u7814\u7a76\u8868\u660e\uff0cSTAT1\u7684\u6fc0\u6d3b\u4e0eMDSCs\u7684\u6291\u5236\u6d3b\u6027\u6709\u5173<\/strong>\u3002STAT1\u5728\u5e72\u6270\u7d20\u03b3\u523a\u6fc0\u4e0b\u88ab\u6fc0\u6d3b\uff0c\u53c2\u4e0e\u8bf1\u5bfc\u578b\u4e00\u6c27\u5316\u6c2e\u5408\u9176\u548c\u7cbe\u6c28\u9178<\/strong>\u7684\u8868\u8fbe\u4e0a\u8c03\u3002Sinha\u7b49\u4eba\u8bc1\u660e\u901a\u8fc7\u5e72\u6270\u7d20\u03b3\u6fc0\u6d3bSTAT1\u5bf9MDSC\u7684\u79ef\u7d2f\u6216\u529f\u80fd\u65e0\u8c03\u8282\u4f5c\u7528\u3002\u968f\u540e\u7684\u7814\u7a76\u96c6\u4e2d\u5728\u5e72\u6270\u7d20\u03b3<\/strong>-STAT1\u901a\u8def\u5728MDSC\u4e9a\u7fa4\u6291\u5236\u6d3b\u6027\u4e2d\u7684\u4f5c\u7528\u3002<\/p>\n

\u6700\u8fd1\u7684\u4e00\u9879\u7814\u7a76\u8868\u660e\uff0cSTAT1<\/strong>\u901a\u8fc7\u589e\u5f3aM-MDSCs\u7684\u6291\u5236\u529f\u80fd\u53d1\u6325\u4e3b\u8981\u4f5c\u7528\u3002\u7136\u800c\uff0c\u901a\u8fc7\u5e72\u6270\u7d20\u03b3\u53d7\u4f53\u6fc0\u6d3bSTAT1\u53ef\u964d\u4f4ePMN-MDSC\u7684\u529f\u80fd\u548c\u5b58\u6d3b\u7387\u3002<\/p>\n

\u8fd9\u4e9b\u7814\u7a76\u8868\u660e\uff0c\u5e72\u6270\u7d20\u03b3-STAT1\u4fe1\u53f7\u901a\u8def\u5728M-MDSCs\u548cPMN-MDSCs\u4e2d\u53ef\u80fd\u5177\u6709\u76f8\u53cd\u7684<\/strong>\u4f5c\u7528\u3002<\/p>\n

\u4e8b\u5b9e\u4e0a\uff0c\u8fd9\u53ef\u4ee5\u89e3\u91ca\u4e3a\u4ec0\u4e48\u6700\u521d\u7684\u7814\u7a76\u6ca1\u6709\u89c2\u5bdf\u5230\u5e72\u6270\u7d20\u03b3\u548c\/\u6216STAT1\u53c2\u4e0eMDSCs\u7684\u6291\u5236\u6d3b\u6027\uff0c\u56e0\u4e3aSinHA\u7b49\u4eba\u7684\u7814\u7a76\u5206\u6790\u4e86\u603bMDSCs(CD11b+<\/sup>Gr-1+<\/sup>)\u7684\u529f\u80fd\uff0c\u800c\u4e0d\u662f\u5355\u72ec\u5206\u6790\u4e9a\u7fa4\u3002<\/p>\n

\u5728\u7f3a\u5c11STAT1\u4fe1\u53f7\u901a\u8def\u7684\u60c5\u51b5\u4e0b\uff0c\u53ef\u80fd\u662fPMN-MDSC\u6570\u91cf\u8f83\u9ad8\uff0c\u800c\u4e0d\u662fM-MDSC\u6570\u91cf\u8f83\u9ad8\uff0c\u4ece\u800c\u89c2\u5bdf\u5230\u4e86\u6291\u5236\u6d3b\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

STAT6<\/strong><\/p>\n

\u53e6\u4e00\u4e2a\u53c2\u4e0eMDSCs\u529f\u80fd\u7684\u8f6c\u5f55\u56e0\u5b50\u662fSTAT6\u3002\u5728MDSCs\u4e2d\uff0cSTAT6\u4fe1\u53f7\u901a\u8def\u5728IL-4\u548cIL-13<\/strong>\u7684\u523a\u6fc0\u4e0b\u901a\u8fc7\u5176\u53d7\u4f53(CD124\u3001IL-4R\u03b1<\/strong>)\u88ab\u6fc0\u6d3b\uff0c\u5bfc\u81f4Arg1\u8868\u8fbe\u4e0a\u8c03<\/strong>\u548c\u4ea7\u751f\u8f6c\u5316\u751f\u957f\u56e0\u5b50-\u03b2<\/strong>\u3002\u6b64\u5916\uff0cSTAT6\u5df2\u88ab\u8bc1\u660e\u53c2\u4e0e\u4e86MDSCs\u7684\u5b58\u6d3b\u548c\u79ef\u805a<\/strong>\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

PGE2<\/strong><\/p>\n

\u524d\u5217\u817a\u7d20\uff0c\u5c24\u5176\u662f\u524d\u5217\u817a\u7d20E2<\/strong>\uff0c\u5728\u80bf\u7624MDSCs\u7684\u6291\u5236\u6d3b\u6027<\/strong>\u4ea7\u751f\u4e2d\u8d77\u7740\u91cd\u8981\u4f5c\u7528\u3002<\/p>\n

Rodriguez\u53ca\u5176\u540c\u4e8b\u53d1\u73b0\uff0c\u901a\u8fc7PGE2\u53d7\u4f53E-\u524d\u5217\u817a\u7d20(EP)4(\u5728MDSCs\u4e2d\u8868\u8fbe)\u53d1\u51fa\u7684\u4fe1\u53f7\u53ef\u8bf1\u5bfcArg1\u7684\u8868\u8fbe\u53ca\u5176\u6d3b\u6027\u3002\u6b64\u5916\uff0cPGE2\u4ea7\u751f\u7684\u4e3b\u8981\u8c03\u8282\u56e0\u5b50COX-2<\/strong>\u7684\u8868\u8fbe\u4e0e\u80bf\u7624\u6d78\u6da6\u6027MDSCs\u4e2dArg1\u548ciNOS<\/strong>\u7684\u8bf1\u5bfc\u76f4\u63a5\u76f8\u5173\u3002<\/p>\n

\u8fd9\u4e9b\u7ed3\u679c\u5f97\u5230\u4e86OberMajer\u7b49\u4eba\u7684\u8bc1\u5b9e\u3002\u4ed6\u4eec\u63cf\u8ff0\u4e86PGE2\u548cCOX-2\u4e4b\u95f4\u7684\u6b63\u53cd\u9988\u5faa\u73af\uff0c\u5bfc\u81f4\u5355\u6838\u7ec6\u80de\u8f6c\u5316\u4e3aM-MDSCs\u3002<\/p>\n

\u5728\u6b64\u57fa\u7840\u4e0a\uff0c\u5229\u7528PGE2\u8bf1\u5bfc\u6291\u5236\u56e0\u5b50\u7684\u4ea7\u751f\uff0c\u4ea7\u751f\u4e86\u4f53\u5916MDSCs\u3002\u5728\u5c0f\u9f20\u95f4\u76ae\u7624\u548c\u80f6\u8d28\u7624\u6a21\u578b\u4e2d\uff0c\u7528COX-2\u6291\u5236\u5242\u6cbb\u7597\u53ef\u6291\u5236MDSCs\u7684\u805a\u96c6\u548c\u529f\u80fd\u3002<\/p>\n

\u6b64\u5916\uff0c\u5728\u63a5\u53d7COX-2\u6291\u5236\u5242\u6cbb\u7597\u7684\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c\u8bc1\u5b9e\u4e86PGE2\u53c2\u4e0e\u4e86MDSC\u7684\u529f\u80fd\uff0c\u8fd9\u4e9b\u60a3\u8005\u7684MDSC\u6837\u7ec6\u80de\u6291\u5236\u6d3b\u6027\u8f83\u4f4e\u3002<\/p>\n

PGE2\u5728\u8c03\u8282MDSCs\u7684\u514d\u75ab\u6291\u5236\u65b9\u9762\u53d1\u6325\u4e86\u4f5c\u7528\uff0c\u4f46\u4e5f\u4e0eMDSCs\u7684\u52df\u96c6\u548c\u79ef\u805a\u6709\u5173\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

HGMB1<\/strong><\/p>\n

HGMB1\u662f\u4e00\u79cdDNA\u7ed3\u5408\u86cb\u767d<\/strong>\uff0c\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u542b\u91cf\u5f88\u9ad8<\/strong>\u3002<\/p>\n

HGMB1\u901a\u8fc7\u4e0eTLR4<\/strong>\u548c\u665a\u671f\u7cd6\u57fa\u5316\u7ec8\u4ea7\u7269\u53d7\u4f53(RAGE<\/strong>)\u7ed3\u5408\u5f71\u54cdMDSC\u3002\u901a\u8fc7\u8fd9\u4e24\u79cd\u53d7\u4f53\u53d1\u51fa\u7684\u4fe1\u53f7\u6fc0\u6d3b\u4e86NF-\u03baB\u901a\u8def<\/strong>\u3002<\/p>\n

Parker\u7b49\u4eba\u7684\u7814\u7a76\u6210\u679c\u8868\u660e\uff0cHGMB1\u901a\u8fc7\u8bf1\u5bfc<\/strong>\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7ec6\u80de\u7684\u81ea\u566c<\/strong>\u6765\u9a71\u52a8MDSCs<\/strong>\u7684\u805a\u96c6\u548c\u6291\u5236\u6d3b\u6027\uff0c\u5e76\u4fc3\u8fdbMDSCs\u7684\u5b58\u6d3b\u3002<\/p>\n

\u6700\u8fd1\uff0cSu\u7b49\u4eba\u8bc1\u660e\uff0c\u5728\u4f53\u5185\uff0c\u7528\u6297HGMB1B\u76d2\u7684\u5355\u514b\u9686\u6297\u4f53\u963b\u65adHGMB1\u53ef\u4ee5\u51cf\u5c11M-MDSCs\u5728\u813e\u810f\u548c\u80bf\u7624\u7ec4\u7ec7\u4e2d\u7684\u79ef\u805a\u3002\u8fd9\u4e9b\u7814\u7a76\u8868\u660e\uff0cHGMB1\u53ef\u80fd\u5728MDSCs\u7684\u79ef\u7d2f\u548c\u529f\u80fd<\/strong>\u4e2d\u8d77\u5173\u952e\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

HIF1\u03b1 <\/strong><\/p>\n

\u65e0\u6c27(\u7f3a\u6c27)<\/strong>\u662f\u80bf\u7624\u5fae\u73af\u5883\u4e0e\u5916\u5468\u6dcb\u5df4\u5668\u5b98\u7684\u6700\u5927\u533a\u522b\u4e4b\u4e00\u3002<\/p>\n

\u7814\u7a76\u8868\u660e\uff0c\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\uff0c\u7f3a\u6c27\u8bf1\u5bfc\u56e0\u5b50-1\u03b1\u80fd\u591f\u4ee5STAT3\u4f9d\u8d56<\/strong>\u7684\u65b9\u5f0f\u8c03\u8282MDSC\u7684\u529f\u80fd\u548cM-MDSCs\u5411TAMs\u7684\u5206\u5316<\/strong>\u3002<\/p>\n

\u6700\u8fd1\uff0c\u8bfa\u66fc\u7b49\u4eba\u63d0\u51fa\u7f3a\u6c27\u8bf1\u5bfc\u56e0\u5b50-1\u03b1\u9009\u62e9\u6027\u5730\u4e0a\u8c03\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u914d\u4f531(PD-L1)<\/strong>\uff0c\u8fd9\u662fMDSC\u4e0a\u7684\u4e00\u79cd\u514d\u75ab\u68c0\u67e5\u70b9\u914d\u4f53 (Fig10.3<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u6700\u8fd1\u7684\u7814\u7a76\u8868\u660e\uff0c\u5185\u8d28\u7f51\u5e94\u6fc0\u53cd\u5e94<\/strong>\u53c2\u4e0e\u4e86MDSCs\u5728\u8377\u7624\u5bbf\u4e3b\u4e2d\u7684\u6291\u5236\u884c\u4e3a\u3002<\/p>\n

\u5185\u8d28\u7f51\u5e94\u6fc0\u53cd\u5e94\u9014\u5f84\uff0c\u4e5f\u88ab\u79f0\u4e3a\u672a\u6298\u53e0\u86cb\u767d\u53cd\u5e94(UPR)\uff0c\u8d1f\u8d23\u5916\u5728\u6216\u5185\u5728\u5e94\u6fc0\u8fc7\u7a0b\u4e2d\u7ef4\u6301\u5185\u8d28\u7f51\u7a33\u6001<\/strong>\u3002<\/p>\n

\u5185\u8d28\u7f51\u5e94\u6fc0\u53cd\u5e94\u7531\u4e09\u4e2a\u5185\u8d28\u7f51\u5b9a\u4f4d\u7684\u8de8\u819c\u86cb\u767d\u4f20\u611f\u5668<\/strong>\u7ec4\u6210\uff1a\u808c\u9187\u9700\u8981\u91761\u03b1(IRE1\u03b1)\u3001\u6fc0\u6d3b\u8f6c\u5f55\u56e0\u5b506\u03b1(ATF6\u03b1)\u548c\u53cc\u94feRNA\u4f9d\u8d56\u6fc0\u9176(PKR)\u6837ER\u76f8\u5173\u6fc0\u9176(PERK)\u3002<\/p>\n

\u8fd9\u4e9bER\u611f\u53d7\u5668\u7684\u6fc0\u6d3b\u5bfc\u81f4\u4e00\u4e9b\u8f6c\u5f55\u56e0\u5b50\u7684\u4e0a\u8c03\uff0c\u5305\u62ec\u526a\u63a5\u7684X-box\u86cb\u767d1(sXBP1)\u3001CCAA T\u589e\u5f3a\u5b50\u7ed3\u5408\u86cb\u767d\u540c\u6e90\u86cb\u767d(CHOP)\u7b49\u3002<\/p>\n

\u4ece\u8377\u7624\u5c0f\u9f20\u548c\u764c\u75c7\u60a3\u8005\u8eab\u4e0a\u5206\u79bb\u7684MDSCs\u90fd\u8fc7\u8868\u8fbe\u51e0\u4e2aER\u5e94\u6fc0\u7684\u6807\u5fd7\u7269\uff0c\u5305sXBP1\u548cCHOP\uff0c\u5e76\u4f34\u968fER\u589e\u5927\uff08ER\u5e94\u6fc0\u7684\u4e00\u4e2a\u6807\u5fd7\uff09\u3002<\/p>\n

\u7528\u5185\u8d28\u7f51\u5e94\u6fc0\u8bf1\u5bfc\u5242thapsigargin\u6cbb\u7597\u7684\u8377\u7624\u5c0f\u9f20\uff0c\u5176MDSCs\u7684\u6570\u91cf\u589e\u52a0<\/strong>\uff0c\u5177\u6709\u5f3a\u5927\u7684\u6291\u5236\u6d3b\u6027<\/strong>\u3002\u6211\u4eec\u53d1\u73b0\uff0c\u7528thapsigargin\u8bf1\u5bfc\u5185\u8d28\u7f51\u5e94\u6fc0\u4ee5IRE1\u03b1\/XBP1\u4f9d\u8d56\u7684\u65b9\u5f0f<\/strong>\u5c06\u6b63\u5e38\u4eba\u4e2d\u6027\u7c92\u7ec6\u80de\u8f6c\u5316\u4e3a\u6291\u5236\u7684PMN-MDSC\u8868\u578b<\/strong>\u3002<\/p>\n

\u9664\u4e86IRE1\u03b1\/XBP1\u5728MDSC\u529f\u80fd\u4e2d\u7684\u4f5c\u7528\u5916\uff0c\u6700\u8fd1\u7684\u7814\u7a76\u53d1\u73b0CHOP\u8fd8\u53c2\u4e0e\u4e86\u80bf\u7624\u76f8\u5173MDSCs\u7684\u6291\u5236\u6d3b\u6027\u3002<\/p>\n

\u4f8b\u5982\uff0cCHOP\u7f3a\u9677\u7684MDSCs\u5931\u53bb\u4e86\u6291\u5236\u529f\u80fd\uff0c\u83b7\u5f97\u4e86\u514d\u75ab\u523a\u6fc0\u8868\u578b\u3002\u5c3d\u7ba1CHOP\u7f3a\u9677\u7684MDSCs\u4e0d\u80fd\u6291\u5236\u4ee5\u975e\u6297\u539f\u7279\u5f02\u6027\u65b9\u5f0f\u523a\u6fc0\u7684T\u7ec6\u80de\uff0c\u4f46\u5b83\u4eec\u4fdd\u7559\u4e86\u963b\u65ad\u6297\u539f\u7279\u5f02\u6027T\u7ec6\u80de\u7684\u80fd\u529b\u3002<\/p>\n

\u76ee\u524d\uff0c\u53ea\u6709IRE1\u03b1\/XBP1\u548cPERK\/CHOP\u4fe1\u53f7\u901a\u8def\u53c2\u4e0e\u4e86MDSCs\u7684\u529f\u80fd\u3002\u7136\u800c\uff0c\u9700\u8981\u66f4\u591a\u7684\u7814\u7a76\u6765\u4e86\u89e3\u5185\u8d28\u7f51\u5e94\u6fc0\u53cd\u5e94\u8c03\u8282MDSCs\u6291\u5236\u6d3b\u6027\u7684\u5177\u4f53\u673a\u5236<\/strong>\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n


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

\n
\n

10.5 MDSCs\u4e0e\u5176\u4ed6\u9ad3\u7cfb\u7ec6\u80de\u7684\u5173\u7cfb<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u591a\u5e74\u6765\uff0c\u6211\u4eec\u5bf9\u764c\u75c7\u4e2d\u9ad3\u7cfb\u7ec6\u80de\u7684\u4e86\u89e3\u63ed\u793a\u4e86\u5b83\u4eec\u5728\u80bf\u7624\u53d1\u751f\u3001\u53d1\u5c55\u548c\u8f6c\u79fb\u4e2d\u7684\u91cd\u8981\u4f5c\u7528\u3002\u7ec8\u672b\u5206\u5316\u7684\u9ad3\u7cfb\u7ec6\u80de<\/strong>\u4e3b\u8981\u6709\u5de8\u566c\u7ec6\u80de<\/strong>\u3001\u6811\u7a81\u72b6\u7ec6\u80de<\/strong>\u548c\u4e2d\u6027\u7c92\u7ec6\u80de<\/strong>\u3002<\/p>\n

\u73b0\u5df2\u6e05\u695a\u7684\u662f\uff0c\u80bf\u7624\u5fae\u73af\u5883<\/strong>\u901a\u8fc7\u5c06\u9ad3\u7cfb\u7ec6\u80de\u963b\u6ede\u5728<\/strong>\u5177\u6709\u5f3a\u5927\u514d\u75ab\u6291\u5236\u6d3b\u6027\u7684\u672a\u6210\u719f\u9636\u6bb5<\/strong>\u6765\u6539\u53d8\u9ad3\u7cfb\u7ec6\u80de\u7684\u5206\u5316\u3002<\/p>\n

\u53e6\u4e00\u4e2a\u53c2\u4e0e\u514d\u75ab\u6291\u5236\u7684\u9ad3\u7cfb\u7ec6\u80de\u662f\u80bf\u7624\u76f8\u5173\u5de8\u566c\u7ec6\u80de(TAM)<\/strong>\uff0c\u5b83\u6765\u6e90\u4e8e\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684\u80bf\u7624\u6d78\u6da6\u6027\u5355\u6838\u7ec6\u80de\u6216M-MDSC<\/strong>\u3002\u7136\u800c\uff0cMDSCs\u4e0e\u5176\u4ed6\u9ad3\u7cfb\u7ec6\u80de\u7684\u5173\u7cfb\u5c1a\u4e0d\u6e05\u695a\u3002<\/p>\n

\u73b0\u9762\u4e34\u7684\u4e3b\u8981\u95ee\u9898\u662f\u7f3a\u4e4fMDSCs\u7684\u7279\u5f02\u6027\u6807\u8bb0\u7269<\/strong>\uff0c\u8fd9\u4f7f\u5f97\u5f88\u96be\u51c6\u786e\u5730\u5c06\u8fd9\u4e9b\u7ec6\u80de\u4e0e\u5355\u6838\u7ec6\u80de\u548c\u4e2d\u6027\u7c92\u7ec6\u80de\u533a\u5206\u5f00\u3002\u8fd9\u5c31\u662f\u4e3a\u4ec0\u4e48\u5728\u4e4b\u524d\u7684\u8bb8\u591a\u7814\u7a76\u4e2d\uff0c\u5177\u6709\u6291\u5236\u6d3b\u6027\u7684MDSC\u6837\u7ec6\u80de\u88ab\u79f0\u4e3a\u5355\u6838\u7ec6\u80de\u548c\u4e2d\u6027\u7c92\u7ec6\u80de\u3002<\/p>\n

\u6700\u8fd1\u7684\u6570\u636e\u5df2\u7ecf\u4e3aMDSCs\u5728\u764c\u75c7\u4e2d\u7684\u7279\u6b8a\u6027\u8d28\u63d0\u4f9b\u4e86\u8bc1\u636e\uff0c\u514d\u75ab\u6291\u5236\u6d3b\u6027<\/strong>\u662fMDSCs\u7684\u56fa\u6709\u7279\u6027\u3002\u4f8b\u5982\uff0c\u5728\u80bf\u7624\u5206\u6ccc\u56e0\u5b50\u5b58\u5728\u7684\u60c5\u51b5\u4e0b\uff0c\u9aa8\u9ad3\u7956\u7ec6\u80de\u53ef\u4ee5\u5728\u4f53\u5916\u4ea7\u751fMDSCs\u3002<\/p>\n

\u4e0eMDSCs\u4e0d\u540c\uff0c\u6210\u719f\u7684\u4e2d\u6027\u7c92\u7ec6\u80de\u6216\u5355\u6838\u7ec6\u80de<\/strong>\u5728\u5b58\u5728\u8fd9\u4e9b\u80bf\u7624\u76f8\u5173\u56e0\u5b50\u7684\u60c5\u51b5\u4e0b\uff0c\u5728\u4f53\u5916\u4e0d\u80fd\u6291\u5236<\/strong>T\u7ec6\u80de\u53cd\u5e94\u3002<\/p>\n

\u51e0\u9879\u6d89\u53ca\u57fa\u56e0\u7ec4\u3001\u86cb\u767d\u8d28\u7ec4\u548c\u8f6c\u5f55\u7ec4\u5206\u6790\u7684\u7814\u7a76\u5df2\u7ecf\u63d0\u4f9b\u4e86\u8bc1\u636e\uff0c\u652f\u6301\u8377\u7624\u5c0f\u9f20PMN-MDSCs\u548c\u4e2d\u6027\u7c92\u7ec6\u80de\u4e4b\u95f4\u7684\u5dee\u5f02\u3002<\/p>\n

\u6b64\u5916\uff0c\u6700\u8fd1\u7684\u4e00\u9879\u7814\u7a76\u63d0\u4f9b\u7684\u4fe1\u606f\u8868\u660e\uff0c\u6839\u636ePMN-MDSCs\u7684\u57fa\u56e0\u56fe\u8c31\uff0cPMN-MDSCs\u4e0d\u540c\u4e8e\u5065\u5eb7\u6350\u8d60\u8005\u6216\u764c\u75c7\u60a3\u8005\u7684\u4e2d\u6027\u7c92\u7ec6\u80de\u3002\u5728\u4eba\u7c7b\u4e2d\uff0cPMN-MDSCs\u53ef\u4ee5\u901a\u8fc7LOX-1\u7684\u8868\u8fbe\u4e0e\u4e2d\u6027\u7c92\u7ec6\u80de\u533a\u5206\u5f00\u6765\uff1b\u5728\u5c0f\u9f20\u4e2d\uff0cLOX-1\u7684\u4f5c\u7528\u5c1a\u4e0d\u6e05\u695a\u3002<\/p>\n

\u5728\u7f3a\u6c27\u7684\u80bf\u7624\u5fae\u73af\u5883<\/strong>\u4e2d\uff0cM-MDSCs\u5206\u5316\u4e3aTAMs<\/strong>\uff0c\u8fd9\u53d7HIF-1\u03b1<\/strong>\u548cSTAT3\u6fc0\u6d3b<\/strong>\u7684\u8c03\u8282\u3002\u4e24\u79cd\u9ad3\u6837\u7ec6\u80de\u90fd\u6709\u5f88\u5f3a\u7684\u514d\u75ab\u6291\u5236\u529f\u80fd\uff0c\u7279\u522b\u662f\u5728\u80bf\u7624\u90e8\u4f4d\uff1b\u7136\u800c\uff0cM-MDSCs\u548cTAMs<\/strong>\u53ef\u4ee5\u901a\u8fc7\u5355\u6838\/\u5de8\u566c\u7ec6\u80de\u76f8\u5173\u6807\u5fd7\u7269\u7684\u53d8\u5316\u6765\u533a\u5206\u3002<\/p>\n

\u5728M-MDSC\u5206\u5316\u4e3aTAMs\u7684\u8fc7\u7a0b\u4e2d\uff0c\u4e3b\u8981\u89c2\u5bdf\u5230F4\/F80\u548cCD115<\/strong>\u8868\u8fbe\u589e\u52a0\uff0cLy6C<\/strong>\u8868\u8fbe\u51cf\u5f31\uff0cIRF8\u548cS100A9\u86cb\u767d<\/strong>\u8868\u8fbe\u964d\u4f4e\u3002<\/p>\n

MDSCs\u5177\u6709\u4e2d\u6027\u7c92\u7ec6\u80de\u548c\u5355\u6838\u7ec6\u80de\u6240\u6ca1\u6709\u7684\u4e00\u4e9b\u751f\u5316\u7279\u5f81\uff0c\u5305\u62ec\u9ad8Arg1\u548ciNOS<\/strong>\u7684\u8868\u8fbe\u548c\u6d3b\u6027\uff0c\u4ee5\u53ca\u9ad8\u6c34\u5e73\u7684ROS\u548cPNT<\/strong>\u4ea7\u751f\u3002<\/p>\n

\u6b64\u5916\uff0c\u6700\u8fd1\u7684\u7814\u7a76\u8868\u660e\uff0cMDSCs\u7684\u5185\u8d28\u7f51\u5e94\u6fc0<\/strong>\u53cd\u5e94\u589e\u52a0\uff0c\u8fd9\u4e0e\u5176\u6291\u5236\u529f\u80fd\u6709\u5173\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u764c\u75c7\u4e2d\u4e0d\u540c\u7c7b\u578b\u7684\u9ad3\u7cfb\u7ec6\u80de\u5f53\u4e2d\uff0c\u76ee\u524d\u5bf9M-MDSCs\u548cTAMs<\/strong>\u4e4b\u95f4\u7684\u5173\u7cfb\u4e86\u89e3\u7684\u66f4\u591a\u4e00\u4e9b\u3002\u6700\u8fd1\u51e0\u4e2a\u5c0f\u7ec4\u7684\u6570\u636e\u663e\u793a\uff0cM-MDSCs<\/strong>\u662f\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684TAM<\/strong>\u524d\u4f53\u7ec6\u80de\u3002<\/p>\n

\u6b64\u5916\uff0c\u5de8\u566c\u7ec6\u80de<\/strong>\u6709\u4e24\u79cd\u6781\u5316\u8868\u578b<\/strong>\uff1a\u5177\u6709\u6297<\/strong>\u80bf\u7624\u7279\u6027\u7684M1\u578b\u5de8\u566c\u7ec6\u80de<\/strong>\u548c\u5177\u6709\u4fc3<\/strong>\u80bf\u7624\u7279\u6027\u7684M2\u5de8\u566c\u7ec6\u80de<\/strong>\u3002\u540e\u8005\u4e0eTAMs<\/strong>\u5173\u7cfb\u66f4\u5bc6\u5207\uff0c\u4f46\u5c1a\u4e0d\u6e05\u695a\u8fd9\u4e24\u79cd\u8868\u578b\u662f\u5426\u662f\u540c\u4e00\u79cd<\/strong>\u5de8\u566c\u7ec6\u80de\u7684\u8868\u578b\uff0c\u4ee5\u53ca\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u8c03\u8282\u5b83\u4eec\u7684\u5206\u5b50\u673a\u5236<\/strong>\u662f\u4ec0\u4e48\u3002<\/p>\n

\u6b64\u5916\uff0c\u5728TAM\u5206\u5316\u4e4b\u524d\uff0c\u5de8\u566c\u7ec6\u80de\u7684\u6781\u5316\u662f\u5426\u7531M-MDSCs<\/strong>\u51b3\u5b9a\u5c1a\u4e0d\u6e05\u695a\u3002\u53e6\u4e00\u65b9\u9762\uff0cPMN-MDSCs<\/strong>\u7684\u6027\u8d28\u53ca\u5176\u4e0e\u4e2d\u6027\u7c92\u7ec6\u80de<\/strong>\u7684\u5173\u7cfb\u4e5f\u662f\u4e0d\u540c\u7814\u7a76\u6301\u7eed\u4e89\u8bba\u7684\u4e3b\u9898\u3002<\/p>\n

\u867d\u7136PMN-MDSCs\u5728\u8be5\u9886\u57df\u88ab\u5e7f\u6cdb\u63a5\u53d7\uff0c\u4f46\u764c\u75c7\u4e2d\u6027\u7c92\u7ec6\u80de\u6781\u5316<\/strong>\u7684\u6982\u5ff5\u63d0\u51fa\u4e86\u8fd9\u6837\u7684\u95ee\u9898\uff1a\u8fd9\u4e9b\u7ec6\u80de\u5728\u75c5\u7406\u4e0a\u662f\u5426\u4e0ePMN-MDSCs<\/strong>\u76f8\u4f3c\uff1f<\/p>\n

\u4e0e\u5de8\u566c\u7ec6\u80de\u76f8\u4f3c\uff0c\u80bf\u7624\u76f8\u5173\u4e2d\u6027\u7c92\u7ec6\u80de(TANs)<\/strong>\u7684\u6982\u5ff5\u7531\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u5177\u6709\u6297\u80bf\u7624(N1\u7ec6\u80de)\u6216\u4eb2\u80bf\u7624(N2\u7ec6\u80de)\u7279\u6027\u7684\u4e2d\u6027\u7c92\u7ec6\u80de\u7ec4\u6210\u3002\u7814\u7a76\u8868\u660e\u8f6c\u5316\u751f\u957f\u56e0\u5b50-\u03b2\u548c1\u578b\u5e72\u6270\u7d20(IFN)<\/strong>\u662f\u8c03\u8282\u764c\u75c7TAN\u53ef\u5851\u6027\u7684\u7ec6\u80de\u56e0\u5b50\u3002<\/p>\n

\u6839\u636e\u5b9a\u4e49\uff0c\u4e2d\u6027\u7c92\u7ec6\u80de\u662f\u77ed\u6682\u7684\u7ec8\u672b\u5206\u5316\u7ec6\u80de\uff0c\u800cPMN-MDSCs\u662f\u672a\u6210\u719f\u7684\u7ec6\u80de\u3002\u56e0\u6b64\uff0c\u5f88\u96be\u60f3\u8c61TANS\u4f1a\u5728\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u88ab\u6781\u5316\u3002<\/p>\n

\u4e8b\u5b9e\u4e0a\uff0c\u51e0\u9879\u7814\u7a76\u8868\u660e\uff0c\u8fd9\u4e9b\u7ec6\u80de\u6709\u80fd\u529b\u6291\u5236<\/strong>\u8377\u7624\u5c0f\u9f20\u7684T\u7ec6\u80de\u53cd\u5e94\uff0c\u8fd9\u652f\u6301\u4e86\u8fd9\u4e9b\u7ec6\u80de\u662fPMN-MDSCs\u7684\u89c2\u70b9\u3002<\/p>\n

\u7136\u800c\uff0cTANs<\/strong>\u7684\u6297\u80bf\u7624\u4f5c\u7528\u5df2\u7ecf\u5728\u764c\u75c7\u60a3\u8005\u4e2d\u6709\u8fc7\u63cf\u8ff0\u3002\u6700\u8fd1\uff0cEruslanov\u7b49\u4eba\u89c2\u5bdf\u5230\u65e9\u671f\u80ba\u764c\u60a3\u8005\u7684TANs\u4e0d\u662f\u514d\u75ab\u6291\u5236\uff0c\u800c\u662f\u523a\u6fc0T\u7ec6\u80de\u53cd\u5e94\uff0c\u8fd9\u9879\u7814\u7a76\u4e3aTANS\u5728\u80bf\u7624\u53d1\u751f\u7684\u65e9\u671f\u9636\u6bb5\u7684\u4f5c\u7528\u63d0\u4f9b\u4e86\u8bc1\u636e\u3002<\/p>\n

\u5f88\u5c11\u6709\u7814\u7a76\u6d89\u53caMDSCs<\/strong>\u5728\u80bf\u7624\u53d1\u751f<\/strong>\u4e2d\u7684\u4f5c\u7528\uff0c\u4ee5\u53ca\u5b83\u5728\u65e9\u671f\u9636\u6bb5<\/strong>\u5982\u4f55\u8c03\u8282\u514d\u75ab\u53cd\u5e94\u3002<\/p>\n

\u4f8b\u5982\uff0cOrtiz\u7b49\u4eba\u7814\u7a76\u8868\u660e\uff0c\u5c0f\u9f20\u66b4\u9732\u5728\u9999\u70df\u70df\u96fe\u4e2d\u4f1a\u5bfc\u81f4\u4e0d\u540c\u5668\u5b98\u4e2d\u975e\u6291\u5236\u6027MDSC\u6837\u7ec6\u80de<\/strong>\u7684\u79ef\u7d2f\u3002\u7136\u800c\uff0c\u5f53\u9999\u70df\u70df\u96fe\u548c\u81f4\u764c\u7269\u8054\u5408\u8d77\u6765\u4fc3\u8fdb\u80ba\u764c\u7684\u53d1\u5c55\u65f6\uff0cMDSCs\u8868\u73b0\u51fa\u5f88\u5f3a\u7684\u514d\u75ab\u6291\u5236\u6d3b\u6027\uff0c\u8fd9\u4e9b\u6570\u636e\u8868\u660eMDSC\u7684\u529f\u80fd\u53d7\u80bf\u7624\u5fae\u73af\u5883\u7684\u63a7\u5236<\/strong>\u3002<\/p>\n

\u6211\u4eec\u5bf9MDSCs\u7684\u6027\u8d28\u4ee5\u53ca\u5b83\u4eec\u5728\u80bf\u7624\u53d1\u5c55\u8fc7\u7a0b\u4e2d\u4e0e\u5176\u4ed6\u9ad3\u7cfb\u7ec6\u80de\u7684\u5173\u7cfb\u7684\u4e86\u89e3\u5c06\u4e3a\u80bf\u7624\u63d0\u4f9b\u65b0\u7684\u6cbb\u7597\u601d\u8def\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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

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10.6 \u9776\u5411MDSCs\u7684\u80bf\u7624\u6cbb\u7597\u7b56\u7565<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6709\u5145\u5206\u7684\u8bc1\u636e\u8868\u660e\uff0cMDSC<\/strong>\u5728\u5916\u5468\u6dcb\u5df4\u5668\u5b98\u548c\u80bf\u7624\u7ec4\u7ec7\u4e2d\u7684\u79ef\u805a\u4e0e\u764c\u75c7\u60a3\u8005\u4e0d\u826f\u7684\u9884\u540e\u548c\u4e34\u5e8a\u7ed3\u679c\u76f8\u5173<\/strong>\u3002<\/p>\n

\u6b64\u5916\uff0cMDSCs\u4e0e\u6297\u764c\u6cbb\u7597\u6709\u5173\uff0c\u5305\u62ec\u53d7\u4f53\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242Sunitinib\u4ee5\u53ca\u51e0\u79cd\u80ba\u764c\u548c\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u7684\u5316\u7597\u836f\u7269\u3002<\/p>\n

\u56e0\u4e3a\u8fd9\u4e9b\u7ec6\u80de\u5177\u6709\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94<\/strong>\u7684\u80fd\u529b\uff0c\u6240\u4ee5\u5305\u62ec\u514d\u75ab\u6cbb\u7597\u5728\u5185\u7684\u764c\u75c7\u6cbb\u7597\u7684\u6548\u679c\u5c06\u53d6\u51b3\u4e8eMDSCs\u7684\u514d\u75ab\u6291\u5236\u4f5c\u7528\u3002<\/p>\n

\u4e8b\u5b9e\u4e0a\uff0c\u4e00\u4e9b\u4e34\u5e8a\u7814\u7a76\u8868\u660eMDSC\u6c34\u5e73\u4e0e\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u5242<\/strong>ipilimumab(\u6297CTLA-4)\u548cnivolumab(\u6297PD-1)\u7684\u53cd\u5e94\u76f8\u5173\u3002<\/p>\n

\u76ee\u524d\uff0c\u968f\u7740\u5bf9\u80bf\u7624\u4e2dMDSCs\u805a\u96c6\u548c\u529f\u80fd\u7684\u5206\u5b50\u673a\u5236\u7684\u4e86\u89e3<\/strong>\u9010\u6e10\u589e\u52a0\uff0c\u4f7f\u5f97\u9488\u5bf9\u8fd9\u4e00\u7ec6\u80de\u7fa4\u4f53\u7684\u6cbb\u7597\u7684\u53ef\u80fd\u6027\u5927\u5927\u63d0\u9ad8\u3002<\/p>\n

\u9488\u5bf9MDSCs\u7684\u4e00\u4e9b\u7b56\u7565\u5305\u62ec(A)\u6d88\u9664<\/strong>MDSCs\uff0c(B)\u963b\u6b62<\/strong>MDSCs\u7684\u79ef\u7d2f\uff0c\u4ee5\u53ca(C)\u706d\u6d3b<\/strong>MDSCs (Fig10.4<\/span>)\u3002\u5176\u4e2d\u51e0\u79cd\u7b56\u7565\u5df2\u7ecf\u5f00\u53d1\u51fa\u6765\uff0c\u76ee\u524d\u6b63\u5728\u4e34\u5e8a\u4e0a\u8fdb\u884c\u6d4b\u8bd5\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6d88\u9664MDSCs<\/strong>\u53ef\u4ee5\u589e\u5f3a\u5305\u62ec\u8fc7\u7ee7\u6027T\u7ec6\u80de\u8f6c\u79fb\u5728\u5185\u7684\u764c\u75c7\u514d\u75ab\u6cbb\u7597\u7684\u6297\u80bf\u7624\u6548\u679c\u3002<\/p>\n

\u4f20\u7edf\u7684\u6297\u764c\u836f\u9664\u4e86\u5bf9\u764c\u7ec6\u80de\u6709\u76f4\u63a5\u4f5c\u7528\u5916\uff0c\u8fd8\u80fd\u4f7f\u80bf\u7624\u5bbf\u4e3b\u4e2dMDSCs\u8017\u7aed<\/strong>\u3002\u5409\u897f\u4ed6\u6ee8<\/strong>\u662f\u7b2c\u4e00\u79cd\u88ab\u62a5\u9053\u80fd\u591f\u5728\u80bf\u7624\u6a21\u578b\u4e2d\u6d88\u9664MDSCs<\/strong>\u7684\u5316\u7597\u836f\u7269\u3002\u8fd9\u9879\u7814\u7a76\u8868\u660e\uff0c\u5409\u897f\u4ed6\u6ee8\u6e05\u9664MDSCs\u53ef\u4ee5\u6539\u5584\u6297\u80bf\u7624\u53cd\u5e94\uff0c\u5e76\u589e\u5f3a\u514d\u75ab\u6cbb\u7597<\/strong>\u7684\u6548\u679c\uff0c\u4ece\u800c\u5bfc\u81f4\u80bf\u7624\u6d88\u9000\u3002<\/p>\n

\u5176\u4ed6\u663e\u793a\u6d88\u9664MDSCs\u7684\u5316\u7597\u836f\u7269\u5305\u62ec5-\u6c1f\u5c3f\u5627\u5576\u3001\u987a\u94c2\u3001\u963f\u9709\u7d20<\/strong>\u7b49\u3002<\/p>\n

\u53e6\u4e00\u79cd\u6d88\u9664MDSCs\u7684\u7b56\u7565\u662f\u4ee5\u80bf\u7624\u574f\u6b7b\u56e0\u5b50<\/strong>\u76f8\u5173\u7684\u51cb\u4ea1\u8bf1\u5bfc\u914d\u4f53\u53d7\u4f53(TRAIL-R<\/strong>)\u4e3a\u9776\u70b9\u3002\u7ed3\u679c\u8868\u660e\uff0cTRAIL-R\uff0c\u5c24\u5176\u662fDR5\u7684\u4e0a\u8c03\u8c03\u8282\u4e86\u80bf\u7624\u5bbf\u4e3b\u4e2dMDSC\u7684\u5b58\u6d3b\uff0c\u5e76\u4e14\u901a\u8fc7\u4f7f\u7528TRAIL-R\u6fc0\u52a8\u5242\uff0cMDSC\u88ab\u9009\u62e9\u6027\u5730\u6d88\u9664\uff0c\u5bfc\u81f4\u80bf\u7624\u751f\u957f\u4ee5CD8+<\/sup>T\u7ec6\u80de\u4f9d\u8d56\u7684\u65b9\u5f0f\u51cf\u5c11\u3002\u4e00\u671f\u8bd5\u9a8c<\/strong>\u7684\u7ed3\u679c\u663e\u793a\uff0c\u83b7\u5f97\u7684\u6570\u636e\u652f\u6301\u5728\u764c\u75c7\u60a3\u8005\u4e2d\u4f7f\u7528TRAIL-R\u6fc0\u52a8\u5242\u3002<\/p>\n

\u6700\u8fd1\uff0c\u4e00\u79cd\u65b0\u7684\u9776\u5411MDSCs<\/strong>\u7684\u6cbb\u7597\u65b9\u6cd5\u88ab\u5f00\u53d1\u51fa\u6765\uff0c\u5b83\u662f\u901a\u8fc7\u5c06S100A9<\/strong>\u884d\u751f\u7684\u591a\u80bd\u4e0e\u6297\u4f53Fc\u90e8\u5206\u8fdb\u884c\u57fa\u56e0\u878d\u5408\u6765\u4ea7\u751f\u591a\u80bd\u6297\u4f53\u3002\u8fd9\u4e9b\u591a\u80bd\u6297\u4f53\u6210\u529f\u5730\u8017\u5c3d\u4e86\u5c0f\u9f20\u6a21\u578b\u8840\u6db2\u3001\u813e\u810f\u548c\u80bf\u7624\u4e2d\u7684MDSCs\u3002<\/p>\n

\u7136\u800c\uff0c\u672a\u6765\u7684\u7814\u7a76\u9700\u8981\u8fdb\u4e00\u6b65\u9610\u660e\u5bfc\u81f4MDSC\u6d88\u9664\u7684\u4f5c\u7528\u673a\u5236(Fig10.4<\/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. 10.4<\/span> \u9488\u5bf9MDSCs\u7684\u6cbb\u7597\u7b56\u7565\u3002\u9776\u5411MDSCs\u7684\u7b56\u7565\u4e3b\u8981\u5305\u62ec\u6d88\u9664\u3001\u706d\u6d3b\u6216\u963b\u65adMDSCs\u7684\u805a\u96c6\u548c\u8bf1\u5bfc\u5206\u5316\u3002\u9996\u5148\uff0c\u4e34\u5e8a\u524d\u548c\u4e34\u5e8a\u7814\u7a76\u8868\u660e\uff0c\u5c0f\u5242\u91cf\u5316\u7597\u836f\u7269\u548cTRAIL\u6fc0\u52a8\u5242\u53ef\u4ee5\u6d88\u9664MDSC\uff0c\u5bfc\u81f4MDSC\u7ec6\u80de\u6b7b\u4ea1\u3002\u5176\u6b21\uff0c\u51e0\u9879\u7814\u7a76\u5df2\u7ecf\u8bc1\u660e\uff0c\u901a\u8fc7\u9776\u5411MDSCs\u7684\u514d\u75ab\u6291\u5236\u673a\u5236\uff0c\u53ef\u4ee5\u5728\u4f53\u5185\u706d\u6d3bMDSCs\u3002PDE5\u3001NO-realizing\u963f\u53f8\u5339\u6797\u3001\u4e09\u841c\u7c7b\u548cCOX-2\u6291\u5236\u5242\u901a\u8fc7\u964d\u4f4eROS\u3001RNS\u548c\u7cbe\u6c28\u9178\u9176\u6c34\u5e73\u6765\u6291\u5236MDSC\u7684\u529f\u80fd\u3002\u6700\u540e\uff0c\u53ef\u4ee5\u901a\u8fc7\u8bf1\u5bfcMDSC\u5206\u5316\u4e3a\u5177\u6709\u514d\u75ab\u523a\u6fc0\u6d3b\u6027\u7684\u7ec8\u672b\u5206\u5316\u7ec6\u80de\u6765\u6291\u5236MDSC\u7684\u805a\u96c6\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

MDSCs\u5229\u7528\u51e0\u79cd\u673a\u5236\u6765\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab<\/strong>\u53cd\u5e94\uff0c\u9488\u5bf9MDSCs\u7684\u6291\u5236\u673a\u5236\u5df2\u7ecf\u5728\u764c\u75c7\u60a3\u8005\u4e2d\u8fdb\u884c\u4e86\u6d4b\u8bd5\u3002<\/p>\n

MDSCs\u4ea7\u751f\u7684ROS\u548cNO<\/strong>\u7684\u589e\u52a0\u5728\u6291\u5236CD8+<\/sup>T\u7ec6\u80de\u5e94\u7b54\u4e2d\u8d77\u91cd\u8981\u4f5c\u7528\u3002\u6d3b\u6027\u6c27\u6e05\u9664\u5242N-\u4e59\u9170\u534a\u80f1\u6c28\u9178(NAC)\u548c\u8fc7\u6c27\u5316\u6c22\u9176\u901a\u5e38\u7528\u4e8e\u4f53\u5916\u68c0\u6d4b\u5c0f\u9f20\u548c\u4ebaMDSCs\u7684\u529f\u80fd\u3002<\/p>\n

NRF2<\/strong>\u662f\u4e00\u79cd\u8f6c\u5f55\u56e0\u5b50\uff0c\u53c2\u4e0e\u6fc0\u6d3b\u6297\u6c27\u5316<\/strong>\u53cd\u5e94\uff0c\u4fdd\u62a4\u7ec6\u80de\u514d\u53d7ROS\u7684\u635f\u4f24\u3002\u4e00\u79cd\u5408\u6210\u7684\u4e09\u841c\u7c7b\u5316\u5408\u7269\u4e0a\u8c03NRF2\u80fd\u591f\u901a\u8fc7\u51cf\u5c11ROS\u7684\u4ea7\u751f\u5e76\u6291\u5236\u5176\u4f53\u5916\u6291\u5236\u529f\u80fd\u6765\u4e2d\u548c\u4eba\u7c7bMDSC\u7684\u6d3b\u6027\u3002<\/p>\n

\u7136\u800c\uff0cBeury\u7b49\u4eba\u6700\u8fd1\u7684\u4e00\u9879\u7814\u7a76\u7ed3\u679c\u663e\u793a\uff0c\u5728\u4e24\u79cd\u5c0f\u9f20\u6a21\u578b\u4e2d\uff0c\u4e0eNRF2+\/+<\/sup>MDSCs\u76f8\u6bd4\uff0cNRF2\u2212\/\u2212<\/sup>MDSCs\u7684\u6291\u5236\u6d3b\u6027\u964d\u4f4e\u3002<\/p>\n

NO\u6e05\u9664\u5242\uff0c\u5982\u7fa7\u57faPTIO(C-PTIO)<\/strong>\uff0c\u6700\u8fd1\u5df2\u7ecf\u88ab\u7528\u4e8e\u68c0\u6d4bMDSCs\u3002\u5728\u8377\u7624\u5c0f\u9f20\u4e2d\uff0cC-PTIO\u6cbb\u7597\u964d\u4f4e\u4e86MDSCs\u7684\u529f\u80fd\uff0c\u63d0\u9ad8\u4e86\u8fc7\u7ee7\u6027T\u7ec6\u80de\u8f6c\u79fb\u7684\u6548\u7387\u3002<\/p>\n

\u9664\u963b\u65adROS\u548cNO\u5916\uff0c\u53e6\u4e00\u79cd\u706d\u6d3bMDSC\u529f\u80fd\u7684\u65b9\u6cd5\u662f\u6291\u5236MDSC\u4e0a\u8c03\u7684\u5206\u89e3\u4ee3\u8c22\u9176<\/strong>\uff0c\u5305\u62ecArg1\u548ciNOS\uff0c\u5b83\u4eec\u4e0e\u6291\u5236T\u7ec6\u80de\u7684\u6fc0\u6d3b\u548c\u589e\u6b96\u6709\u5173\u3002Arg1\u548ciNOS\u6291\u5236\u5242\u5df2\u5e7f\u6cdb\u7528\u4e8eMDSCs\u7684\u529f\u80fd\u68c0\u6d4b\u3002<\/p>\n

Rodriguez\u7b49\u4eba\u7684\u65e9\u671f\u7814\u7a76\u8868\u660e\uff0c\u4e00\u79cd\u9488\u5bf9Arg1<\/strong>\u7684\u7279\u5f02\u6027\u6291\u5236\u5242\uff0cn -\u7f9f\u57fa- nor-l-Arg (nor-NOHA)\uff0c\u53ef\u4ee5\u6291\u5236\u80bf\u7624\u751f\u957f\uff0c\u5e76\u964d\u4f4eMDSCs\u4e2d\u7684Arg1\u6c34\u5e73\u3002\u7cbe\u6c28\u9178(Arg1)\u6291\u5236\u5242\u548c\u8bf1\u5bfc\u578b\u4e00\u6c27\u5316\u6c2e\u5408\u9176(INOS)\u6291\u5236\u5242l-NG-\u5355\u7532\u57fa-l-\u7cbe\u6c28\u9178(l-NMMA)\u5728\u4f53\u5916\u5747\u80fd\u964d\u4f4eMDSC\u529f\u80fd\uff0c\u4fc3\u8fdbT\u7ec6\u80de\u589e\u6b96\u3002<\/p>\n

\u6b64\u5916\uff0c\u764c\u75c7\u60a3\u8005PBMCs<\/strong>\u4e2d\u7684Arg1\u548ciNOS\u6c34\u5e73\u5df2\u663e\u793a\u51fa\u5bf9\u78f7\u9178\u4e8c\u916f\u9176-5(PDE5)\u7684\u53cd\u5e94\u964d\u4f4e\u3002\u51e0\u79cdPDE5\u6291\u5236\u5242\u5df2\u7ecf\u5728\u4e34\u5e8a\u4e0a\u7528\u4e8e\u6cbb\u7597\u764c\u75c7\u548c\u5176\u4ed6\u75be\u75c5\uff0c\u53ef\u4f7fMDSC\u6570\u91cf\u51cf\u5c11\u3002<\/p>\n

\u6700\u8fd1\uff0c\u4e00\u4efd\u4e34\u5e8a\u62a5\u544a\u8868\u660e\uff0c\u63a5\u53d7PDE5\u6291\u5236\u5242\u4ed6\u8fbe\u62c9\u975e\u6cbb\u7597\u7684\u5934\u9888\u90e8\u764c\u75c7\u60a3\u8005\uff0cMDSCs\u51cf\u5c11\uff0cArg1\u548ciNOS\u8868\u8fbe\u51cf\u5c11\uff0cT\u7ec6\u80de\u589e\u52a0\u3002<\/p>\n

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CCL2\u785d\u5316<\/strong>\u5bfc\u81f4\u80bf\u7624\u5fae\u73af\u5883\u5185CD8+<\/sup>T\u7ec6\u80de\u589e\u52a0\u3002MDSCs\u514d\u75ab\u6291\u5236\u7684\u53e6\u4e00\u4e2a\u4e3b\u8981\u673a\u5236\u662f\u901a\u8fc7\u6fc0\u6d3bCOX-2<\/strong>\u4ea7\u751fPGE2\u3002\u51e0\u79cdCOX-2\u6291\u5236\u5242\uff0c\u5305\u62ec\u585e\u6765\u6614\u5e03\uff0c\u5df2\u7ecf\u5728\u4e0d\u540c\u5c0f\u9f20\u6a21\u578b\u7684MDSCs\u4e2d\u663e\u793a\u51faPGE2\u7684\u4ea7\u751f\u51cf\u5c11\u4ee5\u53caArg1\u548ciNOS\u7684\u6291\u5236\u3002<\/p>\n

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\u63a5\u53d7ATRA\u6cbb\u7597\u7684\u764c\u75c7\u60a3\u8005\u7684\u9ad3\u7cfb\/\u6dcb\u5df4\u7cfb\u6811\u7a81\u72b6\u7ec6\u80de\u6bd4\u7387\u548c\u514d\u75ab\u53cd\u5e94\u5747\u6709\u6539\u5584\u3002ATRA\u8bf1\u5bfcMDSC\u5206\u5316\u7684\u673a\u5236\u6d89\u53caERK1\/ERK2 MAPK\u6fc0\u9176\u7684\u6fc0\u6d3b\uff0c\u8be5\u6fc0\u9176\u4e0a\u8c03\u8c37\u80f1\u7518\u80bd\u5408\u6210\u9176\u7684\u8868\u8fbe\uff0c\u589e\u52a0\u8c37\u80f1\u7518\u80bd\u7684\u5408\u6210\u3002ATRA\u5728MDSCs\u4e2d\u79ef\u7d2f\u8c37\u80f1\u7518\u80bd\uff0c\u964d\u4f4eROS\u6c34\u5e73\uff0c\u5bfc\u81f4MDSC\u5206\u5316\u4e3a\u6210\u719f\u7684\u9ad3\u6837\u7ec6\u80de\u3002\u5728\u5e7f\u6cdb\u671f\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u4e2d\uff0cATRA\u901a\u8fc7\u8017\u5c3dMDSCs\u589e\u5f3a\u4e86\u764c\u75c7\u75ab\u82d7\u7684\u6548\u679c\u3002\u6b64\u5916\uff0c\u5728\u8089\u7624\u6a21\u578b\u4e2d\uff0cATRA\u6cbb\u7597\u663e\u793aMDSC\u6c34\u5e73\u548c\u529f\u80fd\u964d\u4f4e\uff0c\u6539\u5584\u5d4c\u5408\u6297\u539f\u53d7\u4f53(CAR)\u6cbb\u7597\u53cd\u5e94\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\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><\/section>\n
f<\/span>or Cancer Immunotherapy<\/span><\/section>\n
\u4f5c\u8005 | Kevin Alicea-Torres and Dmitry I. Gabrilovich<\/span><\/section>\n
\u7ffb\u8bd1 |   \u90ed\u5b50 \u848b\u4fca\u535a \u949f\u96ea\u83b9<\/span><\/section>\n
\u7f16\u8f91\u6392\u7248 | \u7f57\u4f73\u4f73<\/span><\/span><\/section>\n
\u521d\u5ba1 | \u5ed6\u5a9b \u4efb\u632f\u9633<\/span><\/section>\n
\u7ec8\u5ba1 | \u8096\u5efa\u52c7 \u738b\u5764<\/span><\/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<\/p>\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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