{"id":35704,"date":"2020-10-06T00:18:02","date_gmt":"2020-10-05T16:18:02","guid":{"rendered":"https:\/\/case.ntu.edu.tw\/blog\/?p=35704"},"modified":"2020-09-22T11:23:20","modified_gmt":"2020-09-22T03:23:20","slug":"%e5%a4%a7%e8%85%b8%e7%99%8c%e7%9a%84%e5%85%8d%e7%96%ab%e7%99%82%e6%b3%95","status":"publish","type":"post","link":"https:\/\/case.ntu.edu.tw\/blog\/?p=35704","title":{"rendered":"\u5927\u8178\u764c\u7684\u514d\u75ab\u7642\u6cd5"},"content":{"rendered":"

\u514d\u75ab\u7642\u6cd5\u53ef\u85c9\u7531\u6291\u5236\u764c\u7d30\u80de\u9003\u907f\u4eba\u9ad4\u514d\u75ab\u7d30\u80de\u6bd2\u6bba\u7684\u6a5f\u5236\uff0c\u800c\u4f7f\u5f97\u764c\u7d30\u80de\u5728\u514d\u75ab\u7cfb\u7d71\u4f5c\u7528\u4e0b\u88ab\u6d88\u6ec5\uff0c\u5c0d\u65bc\u6709\u57fa\u56e0\u578bMSI-H\uff08microsatellite instability-high\uff09\/dMMR\uff08defective match repair\uff09\u5b58\u5728\u7684\u5927\u8178\u764c\u60a3\u8005\u800c\u8a00\u53ef\u8b02\u662f\u53e6\u4e00\u7a2e\u6cbb\u7642\u7684\u9078\u64c7\u3002\u8fd1\u5e74\u6709\u8cf4\u65bc\u5927\u8178\u816b\u7624\u7d30\u80de\u7684\u57fa\u56e0\u578b\u614b\u53ca\u5206\u5b50\u751f\u7269\u5b78\u4f5c\u7528\u6a5f\u5236\u7684\u9010\u6f38\u660e\u6717\u5316\uff0c\u8b93\u514d\u75ab\u7642\u6cd5\u7684\u7cbe\u6e96\u91ab\u7642\uff08precision medicine\uff09\u53ef\u4ee5\u63d0\u4f9b\u60a3\u8005\u91cf\u8eab\u8a02\u88fd\u7684\u500b\u4eba\u5316\u6cbb\u7642\u8655\u65b9\uff0c\u4f7f\u7642\u6548\u6700\u5927\u5316\u800c\u526f\u4f5c\u7528\u6700\u5c0f\u5316\uff0c\u6709\u6f5b\u529b\u4f7f\u5f97\u8f49\u79fb\u6027\u5927\u8178\u764c\u4e0d\u518d\u662f\u7d55\u75c7\uff0c\u7d66\u75c5\u4eba\u5e36\u4f86\u75be\u75c5\u6cbb\u7652\u7684\u4e00\u7dda\u66d9\u5149\u3002<\/strong><\/span><\/p>\n

\"\"
\u5716\u7247\u4f86\u6e90: Pixabay<\/figcaption><\/figure>\n

\u64b0\u6587\uff0f\u9673\u6df5\u9293<\/strong><\/p>\n

\u5927\u8178\u764c\u7684\u50b3\u7d71\u6cbb\u7642\u65b9\u5f0f<\/strong><\/span><\/p>\n

\u5927\u8178\u764c\u7684\u6cbb\u7642\u5728\u524d\u671f\u4ee5\u624b\u8853\u5207\u9664\u70ba\u4e3b\uff0c\u53ef\u80fd\u4f9d\u75c5\u60c5\u7684\u72c0\u6cc1\u518d\u914d\u5408\u5316\u5b78\u548c\/\u6216\u653e\u5c04\u7dda\u6cbb\u7642\u3002\u6839\u64da\u75c5\u4eba\u7684\u5e74\u9f61\u3001\u5065\u5eb7\u60c5\u5f62\u3001\u75be\u75c5\u671f\u5225\u3001\u816b\u7624\u5927\u5c0f\u53ca\u4f4d\u7f6e\u4f86\u63a1\u7528\u6700\u9069\u7576\u7684\u6cbb\u7642\uff0c\u4e3b\u8981\u7684\u65b9\u6cd5\u5982\u4e0b: (1)\u5fae\u5275\u624b\u8853\uff1a\u900f\u904e\u8179\u8154\u5167\u8996\u93e1\u9ad8\u89e3\u6790\u5ea6\u7684\u93e1\u982d\uff0c\u53ef\u660e\u78ba\u7684\u5c07\u5927\u8178\u76f4\u8178\u816b\u7624\u53ca\u5468\u570d\u5c40\u90e8\u7684\u6dcb\u5df4\u7d50\u5b9a\u4f4d\uff0c\u4e26\u9032\u884c\u5b8c\u6574\u7684\u5207\u9664\u3002(2)\u5316\u5b78\u6cbb\u7642\uff1a\u76ee\u524d\u4ee5\u4f7f\u7528Fluorouracil\uff085-Flurouracie, 5-FU\uff09\u52a0\u4e0aLeucovorin\u70ba\u4e3b\uff0c\u7642\u6548\u4f9d\u6295\u4e88\u7684\u65b9\u6cd5\u53ca\u5291\u91cf\u800c\u6709\u5dee\u7570\u3002(3)\u653e\u5c04\u7dda\u6cbb\u7642\uff1a\u82e5\u8a55\u4f30\u5927\u8178\u764c\u7d30\u80de\u5df2\u4fb5\u5165\u8178\u58c1\u6f3f\u819c\u5c64\u4ee5\u4e0a\u6216\u5df2\u8f49\u79fb\u5230\u5c40\u90e8\u6dcb\u5df4\u7d50\uff0c\u6703\u5148\u4f5c\u653e\u5c04\u6cbb\u7642\u4e26\u914d\u5408\u5316\u5b78\u6cbb\u7642\uff0c\u4ee5\u907f\u514d\u5c40\u90e8\u5fa9\u767c\uff0c\u66f4\u6709\u7e2e\u5c0f\u816b\u7624\u7684\u6548\u679c\u3002(4)\u6a19\u9776\u6cbb\u7642\uff1a\u764c\u601d\u505c(Avastin; Bevacizumab) \u662f\u4e00\u7a2e\u5c0d\u6297\u8840\u7ba1\u5167\u76ae\u589e\u751f\u56e0\u5b50\u7684\u55ae\u682a\u6297\u9ad4\uff0c\u5e38\u8207\u5176\u4ed6\u5316\u5b78\u7642\u6cd5\u5408\u4f75\u4f7f\u7528\uff0c\u4f5c\u70ba\u8f49\u79fb\u6027\u5927\u8178\u764c\uff08metastatic colonrectal cancer, mCRC\uff09\u7684\u7b2c\u4e00\u7dda\u6cbb\u7642\uff1b\u723e\u5fc5\u5f97\u8212(Erbitux; Cetuximab)\u662f\u4e00\u7a2e\u963b\u65b7\u8868\u76ae\u751f\u9577\u56e0\u5b50\u7684\u55ae\u682a\u6297\u9ad4\uff0c\u53ef\u6291\u5236\u816b\u7624\u7d30\u80de\u589e\u6b96\uff0c\u4e26\u5c0e\u81f4\u7d30\u80de\u51cb\u4ea1(apoptosis)\uff1b\u764c\u745e\u683c\uff08Stivarga; Regorafenib\uff09\u662f\u4e00\u7a2e\u53e3\u670d\u591a\u91cd\u6fc0\u9176\u6291\u5236\u5291\uff08 multi-kinase inhibitor\uff09\uff0c\u5177\u6709\u6291\u5236\u8840\u7ba1\u65b0\u751f\u3001\u816b\u7624\u589e\u751f\u53ca\u764c\u7d30\u80de\u8f49\u79fb\u7684\u529f\u6548\uff0c\u9069\u7528\u65bc\u6cbb\u7642mCRC\u3002<\/p>\n

\u8aa4\u914d\u4fee\u5fa9\u53ca\u6709\u7f3a\u5931\u7684\u914d\u5c0d\u4fee\u88dc<\/strong><\/span><\/p>\n

\u932f\u914d\u4fee\u5fa9\uff08mismatch repair, MMR\uff09\u86cb\u767d\u8ca0\u8cac\u4fee\u88dcDNA\u5408\u6210\u9176\uff08polymerase\uff09\u5728DNA\u5408\u6210\u904e\u7a0b\u6240\u767c\u751f\u7684\u932f\u8aa4\uff0c\u5982\u679c\u7f3a\u4e4f\u9019\u7a2e\u86cb\u767d\uff0c\u4fbf\u6703\u5c0e\u81f4\u5fae\u885b\u661f\uff08\u4e00\u7a2e\u77ed\u4e14\u91cd\u8907\u7684DNA\u5e8f\u5217\uff09\u4e0d\u7a69\u5b9a\uff08microsatellite instability, MSI\uff09\u7684\u932f\u8aa4\uff08error\uff09\uff0c\u5229\u7528\u514d\u75ab\u7d44\u7e54\u5316\u5b78\uff08immunohistochemistry\uff09\u67d3\u8272\u6216\u805a\u5408\u9176\u9023\u9396\u53cd\u61c9\uff08polymerase chain reaction\uff09\u53ef\u6aa2\u6e2c\u4e0d\u7a69\u5b9a\u548c\u7e2e\u77ed\u7684\u5fae\u885b\u661f\u4f86\u5f97\u77e5MSI\u767c\u751f\u7684\u72c0\u6cc1\u3002\u9ad8\u5fae\u885b\u661f\u4e0d\u7a69\u5b9a\uff08microsatellite instability-high, MSI-H\uff09\u7684\u816b\u7624\u4e43\u56e0\u7f3a\u5c11MMR\u86cb\u767d\u800c\u5c0e\u81f4\u5fae\u885b\u661f\u7e2e\u77ed\u548c\/\u6216\u4e0d\u7a69\u5b9a\u3002\u5728\u81e8\u5e8a\u4e0a\uff0c\u767c\u73fe\u5927\u8178\u764c\u60a3\u8005\u9808\u5e36\u6709MSI-H\u6216\u6709\u7f3a\u5931\u7684\u914d\u5c0d\u4fee\u88dc\uff08defective match repair, dMMR\uff09\u7684\u57fa\u56e0\u578b\uff0c\u9032\u884c\u514d\u75ab\u6cbb\u7642\u624d\u6709\u6548\u679c\u3002<\/p>\n

\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7528\u65bc\u6cbb\u7642\u5927\u8178\u764c<\/strong><\/span><\/p>\n

\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\uff08immune checkpoint inhibitor\uff09\u7684\u4f7f\u7528\u6539\u8b8a\u4e86\u591a\u7a2e\u75be\u75c5\u7684\u6cbb\u7642\u65b9\u6cd5\u548c\u7d50\u679c\uff0c\u4f8b\u5982\u80ba\u764c\u3001\u814e\u764c\uff0c\u8180\u80f1\u764c\u3001\u9ed1\u8272\u7d20\u7624\u53ca\u970d\u5947\u91d1\u6c0f\u75c7\uff08Hodgkin's lymphoma\uff09\u7b49\uff0c\u4f46mCRC\u9bae\u5c11\u5c0d\u9019\u7a2e\u514d\u75ab\u7642\u6cd5\u7522\u751f\u53cd\u61c9\u3002\u5118\u7ba1\u5982\u6b64\uff0c\u7f8e\u570b\u98df\u54c1\u85e5\u7269\u7ba1\u7406\u5c40\uff08Food and Drug Administration, FDA\uff09\u9084\u662f\u57282014\u5e74\u6279\u51c6\u4e86\u4f7f\u7528\u7a0b\u5e8f\u6027\u7d30\u80de\u6b7b\u4ea1\u86cb\u767d1\uff08program cell death protein 1, PD-1\uff09\u6291\u5236\u5291pembrolizumab\uff08Keytruda\uff09\u548cnivolumab\uff08Opdivo\uff09\u7528\u65bc\u542b\u6709MSI-H\u7684\u816b\u7624\u53camCRC\u7684\u81e8\u5e8a\u6cbb\u7642\u3002\u7531\u65bcPD-1\u6703\u8ca0\u5411\u8abf\u7bc0\u764c\u7d30\u80de\u5c0d\u8eab\u9ad4\u5167\u7684\u514d\u75ab\u53cd\u61c9\uff0c\u6545\u5728PD-1\u548c\u816b\u7624\u7684\u7a0b\u5e8f\u6027\u7d30\u80de\u6b7b\u4ea1\u86cb\u767d\u914d\u9ad41\uff08program cell death protein ligand-1, PD-L1\uff09\u589e\u52a0\u6642\uff0c\u816b\u7624\u53ef\u9003\u904e\u514d\u75ab\u7cfb\u7d71\u7684\u653b\u64ca\u3002\u56e0\u6b64\uff0c\u7814\u7a76\u4eba\u54e1\u4f5c\u51fa\u4e00\u500b\u5047\u8a2d\uff1a\u300c\u5df2\u77e5PD-1\u6291\u5236\u5291\u53ef\u4ee5\u6fc0\u6d3b\u8eab\u9ad4\u5c0d\u764c\u7d30\u80de\u7684\u514d\u75ab\u53cd\u61c9\uff0c\u56e0\u70ba\u5728\u816b\u7624\u4fb5\u8972\u7684\u5340\u57df\u6703\u7522\u751f\u5927\u91cf\u7684\u65b0\u6297\u539f\uff08neoantigen\uff09\u3001\u816b\u7624\u6d78\u6f64\u6dcb\u5df4\u7d30\u80de\uff08tumor infiltrating lymphocyte\uff09\u53ca\u76f8\u95dc\u7684\u514d\u75ab\u6d78\u6f64\uff08immune infiltrate\uff09\uff0c\u4f7f\u5f97PD-1\u6291\u5236\u5291\u5c0dMSI-H\u7684\u764c\u75c7\u6703\u7279\u5225\u6709\u6548\u300d\u3002\u5728\u7b2c\u4e8c\u671f\u7684\u81e8\u5e8a\u8a66\u9a57\u4e2d\uff0c\u4ed6\u5011\u4f7f\u7528pembrolizumab\u6cbb\u7642MSI-H\u7684mCRC\u3001\u5fae\u885b\u661f\u7a69\u5b9a\uff08microsatellite stable, MSS\uff09mCRC\u53caMSI-H\u7684\u5be6\u9ad4\u816b\u7624\u60a3\u8005\uff0c\u7d50\u679c\u767c\u73fe\u53ea\u6709MSI-H\u7684mCRC\u548cMSI-H\u5be6\u9ad4\u816b\u7624\u7684\u60a3\u8005\u7522\u751f\u6301\u4e45\u6027\u7684\u53cd\u61c9\uff0c\u800c\u4e14\u5b58\u6d3b\u7387\u6709\u986f\u8457\u6539\u5584\uff0c\u6b64\u5916pembrolizumab\u548cnivolumab\u975c\u8108\u7d66\u85e5\u7684\u6574\u9ad4\u8010\u53d7\u6027\u512a\u65bc\u5316\u7642\u85e5\u7269\u3002<\/p>\n

\u5927\u8178\u764c\u514d\u75ab\u7642\u6cd5\u65b0\u6a19\u9776\u7684\u958b\u767c<\/strong><\/span><\/p>\n

\u8da8\u5316\u56e0\u5b50\u53d7\u9ad48\uff08chemokine (C-C motif) receptor 8, CCR8\uff09\u662f\u5728\u8abf\u7bc0\u6027T\u7d30\u80de\uff08regulatory T cell, Treg\uff09\u4e0a\u8868\u9054\u7684\u4e00\u7a2e\u53d7\u9ad4\uff0c\u5df2\u77e5\u5c0dCCR8 + Treg\u4ecb\u5c0e\u7684\u514d\u75ab\u6291\u5236\u81f3\u95dc\u91cd\u8981\u3002\u6700\u8fd1\u7684\u7814\u7a76\u986f\u793a\uff0c\u8207\u6b63\u5e38\u7d44\u7e54\u7684\u99d0\u7559\uff08tissue-resident\uff09Treg\u76f8\u6bd4\uff0cCCR8\u5728\u4e73\u764c\u3001\u5927\u8178\u764c\u53ca\u80ba\u764c\u60a3\u8005\u7684\u816b\u7624\u99d0\u7559\uff08tumor-resident\uff09Treg\u4e2d\u7279\u5225\u9ad8\u3002\u56e0\u6b64\uff0cCCR8\u53ef\u80fd\u6210\u70ba\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u7684\u5408\u7406\u9776\u6a19\uff0c\u7528\u65bc\u8abf\u63a7\u99d0\u7559\u816b\u7624\u7684Treg\u4ee5\u589e\u5f37\u6297\u816b\u7624\u7684\u514d\u75ab\u53cd\u61c9\uff0c\u4e26\u5ef6\u9577\u75c5\u4eba\u7684\u5b58\u6d3b\u671f\u3002<\/p>\n

\u57282018\u5e74\uff0c\u7f8e\u570b\u7814\u7a76\u4eba\u54e1\u5728\u52d5\u7269\u5be6\u9a57\u4e2d\u8b49\u660e\u4e86\u91dd\u5c0dCCR8\u7684\u55ae\u682a\u6297\u9ad4\uff08monoclonal antibody\uff09\u53ef\u4ee5\u986f\u8457\u6291\u5236\u816b\u7624\u751f\u9577\uff0c\u4e26\u6539\u5584\u7f79\u60a3\u5927\u8178\u816b\u7624\u5c0f\u9f20\u7684\u9577\u671f\u5b58\u6d3b\u7387\uff0c\u9019\u7a2e\u6297\u816b\u7624\u6d3b\u6027\u7684\u7522\u751f\u8207\u6297\u816b\u7624\u7279\u7570\u6027T\u7d30\u80de\u7684\u589e\u52a0\u3001CD4 +T\u7d30\u80de\u548cCD8 + T\u7d30\u80de\u6d78\u6f64\u7684\u589e\u5f37\u53ca\u816b\u7624\u99d0\u7559CD4 + CCR8 + Treg\u7684\u51fa\u73fe\u983b\u7387\u986f\u8457\u964d\u4f4e\u6709\u5bc6\u5207\u95dc\u4fc2\u3002\u7814\u7a76\u7d50\u679c\u986f\u793aCCR8\u5177\u6709\u6f5b\u529b\u4f5c\u70ba\u5927\u8178\u764c\u514d\u75ab\u7642\u6cd5\u7684\u65b0\u6a19\u9776\uff0c\u9776\u5411\u4f5c\u7528\u5230CCR8\u53ef\u6709\u6548\u6e1b\u5c11\u5927\u8178\u816b\u7624\u99d0\u7559Treg\u3002\u9019\u500b\u767c\u73fe\u610f\u5473\u8457CCR8\u7684\u963b\u65b7\u5291\uff08blockade\uff09\u6216\u6d88\u8017\u6297\u9ad4\uff08depletion antibody\uff09\u5728\u81e8\u5e8a\u4e0a\u53ef\u80fd\u53ef\u4ee5\u7528\u65bc\u6cbb\u7642\u591a\u7a2e\u764c\u75c7\uff0c\u7121\u8ad6\u662f\u4f5c\u70ba\u55ae\u4e00\u7642\u6cd5\u6216\u8207\u5176\u4ed6\u514d\u75ab\u7642\u6cd5\u806f\u5408\u4f7f\u7528\u5747\u5177\u6709\u76f8\u7576\u524d\u666f\u3002<\/p>\n

\u7d50\u8ad6<\/strong><\/span><\/p>\n

\u514d\u75ab\u6cbb\u7642\u662f\u4e00\u7a2e\u4f5c\u7528\u6a5f\u8f49\u8207\u50b3\u7d71\u6cbb\u7642\u65b9\u6cd5\u622a\u7136\u4e0d\u540c\u7684\u6297\u764c\u6cd5\uff0c\u539f\u7406\u662f\u4ee5\u85e5\u7269\u300c\u6aa2\u67e5\u300d\u81ea\u8eab\u7684\u514d\u75ab\u7cfb\u7d71\uff0c\u5c07\u6703\u5f71\u97ffT\u7d30\u80de\u514d\u75ab\u6aa2\u67e5\u9ede\u529f\u80fd\u7684\u7269\u8cea\u52a0\u4ee5\u6e05\u9664\uff0c\u6062\u5fa9T\u7d30\u80de\u8fa8\u8b58\u764c\u7d30\u80de\u7684\u80fd\u529b\uff0c\u9032\u800c\u653b\u64ca\u4e4b\u3002\u5df2\u77e5\u53ef\u9032\u884c\u514d\u75ab\u6cbb\u7642\u7684\u5927\u8178\u764c\u60a3\u8005\uff0c\u9808\u5728\u816b\u7624\u7d30\u80de\u57fa\u56e0\u578b\u5206\u985e\u5177\u6709MSI-H\u6216dMMR\u7684\u689d\u4ef6\u4e0b\uff0c\u96d6\u9069\u5408\u8005\u4e0d\u591a\uff08\u7d045%\uff09\u4e14\u76ee\u524d\u81e8\u5e8a\u4e0a\u53cd\u61c9\u7387\u4e0d\u76e1\u7406\u60f3\uff0c\u4f46\u96a8\u8457\u5c0d\u816b\u7624\u5206\u5b50\u751f\u7269\u5b78\u7684\u65b0\u7406\u89e3\u53ca\u65b0\u6a19\u9776\u7684\u958b\u767c\uff0c\u514d\u75ab\u7642\u6cd5\u6709\u671b\u6210\u70ba\u5927\u8178\u764c\u6cbb\u7642\u7684\u65b0\u986f\u5b78\uff0c\u70ba\u50b3\u7d71\u6cbb\u7642\u6548\u679c\u4e0d\u4f73\u7684\u60a3\u8005\u63d0\u4f9b\u65b0\u7684\u6cbb\u7642\u9078\u64c7\uff0c\u5e36\u4f86\u75be\u75c5\u5eb7\u5fa9\u7684\u65b0\u5951\u6a5f\u3002<\/p>\n

 <\/strong><\/p>\n

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

    \n
  1. Stein A, Folprecht G. Immunotherapy of colon cancer. Oncol Res Treat. 2018;41(5):282-285. doi: 10.1159\/000488918. Epub 2018 Apr 26.<\/li>\n
  2. Wu C. Systemic therapy for colon cancer. Surg Oncol Clin N Am. 2018 Apr;27(2):235-242. doi: 10.1016\/j.soc.2017.11.001. Epub 2017 Dec 16.<\/li>\n
  3. Villarreal DO, L'Huillier A, Armington S, Mottershead S,Filippova EV, Coder BD, Petit RG, Princiotta MF. Targeting CCR8 induces protective antitumor immunity and enhances vaccine-induced responses in colon cancer. Cancer Res. 2018 Sep 15;78(18):5340-5348. doi: 10.1158\/0008-5472.CAN-18-1119. Epub 2018 Jul 19.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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