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Cell research：抗肿瘤免疫疗法中的个体化医疗

2015-01-28 佚名 生物谷

肿瘤免疫疗法
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cytotoxic T lymphocyte antigen-4 (CTLA-4)的阻断型抗体ipilimumab能够在一部分黑色素瘤患者中引起免疫反应，从而达到一致肿瘤生长的效果。然而，作为一类有效地免疫诱导药物，目前临床上还没有指示这一药物治疗效果的人体生物标志。最近法国Gustave-Roussy癌症研究所Laurence Zitvogel课题组等在cell research杂志在线发表了他

cytotoxic T lymphocyte antigen-4 (CTLA-4)的阻断型抗体ipilimumab能够在一部分黑色素瘤患者中引起免疫反应，从而达到一致肿瘤生长的效果。然而，作为一类有效地免疫诱导药物，目前临床上还没有指示这一药物治疗效果的人体生物标志。最近法国Gustave-Roussy癌症研究所Laurence Zitvogel课题组等在cell research杂志在线发表了他们对ipilimumab免疫疗法中相关分子标记的研究。
 
CTLA-4是T细胞表面的一类负向调节分子，阻断CTLA-4的信号后，理论上T细胞受到的负向调控信号会大幅减弱，免疫效应会进而增强。T细胞激活后会表达大量效应性的细胞因子，比如IL-2，IFN-γ等。
 
首先，作者检测了IL-2R在ipilimumab治疗过程中的影响。结果显示：当使用抗体阻断IL-2，IL-15（两者均与IL-2Rβγ受体结合），或直接阻断受体IL-2Rα与IL-2Rβ时，ipilimumab对免疫治疗的效果就被抑制了。之后，作者发现当使用soluble CD122（一类与IL-2竞争性结合IL-2Rβ的蛋白）联合ipilimumab用药时，患癌小鼠的各项抗肿瘤生理指标（包括效应T细胞比例，IFN-γ分泌浓度，肿瘤体积等）均发生了明显下降。以上结果说明IL-2R的缺失会抑制ipilimumab的处理带来的免疫反应的强化。
 
之后，作者通过人为注射重组IL-2，发现IL-2可以增强ipilimumab的抗癌效果。进一步研究发现，在生理条件下，ipilimumab对CTLA-4的抑制可以间接促进IL-2的释放，同时在药物刺激下肿瘤部位会富集大量CD4+Lag3+的效应T细胞。作者认为IL-2可能是由这部分CD4+Lag3+T细胞释放的。在比较了CD4+Lag3+T细胞与其它亚群T细胞在接受CTLA-4的刺激后IL-2的表达水平。结果显示，CD4+Lag3+T细胞在刺激后IL-2的表达量（约15被）远高于其它类群的细胞，同时细胞FoxP3表达量明显下调。以上结果说明CD4+Lag3+T细胞是ipilimumab治疗后的主要效应T细胞。
 
CD25是另一类可以与IL-2R结合抑制IL-2信号传递的分子。作者发现转移性黑色素瘤的患者在接受ipilimumab与rIL-2治疗后的血清中CD25的表达水平会有明显升高。作者人为地向模型小鼠注射sCD25, 结果显示sCD25的人为提高会导致小鼠体内Treg的增多。其他一些证据也显示CD25会抑制ipilimumab的引起的免疫激活效果。
 
最后，作者分析了患者中sCD25的水平与其寿命的相关性。结果显示，sCD25水平高的患者其寿命要短于相对较低的患者。因此，他们认为sCD25可以作为一类ipilimumab针对性的生物标志来判断ipilimumab是否对某一患者的治疗是否有效。
 
原始出处
 
Hannani D1, Vétizou M1, Enot D2, Rusakiewicz S3, Chaput N3, Klatzmann D4, Jacquelot N1, Vimond N3, Chouaib S5, Mateus C6, Allison JP7, Ribas A8, Wolchok JD9, Yuan J9, Wong P9, Postow M9, Mackiewicz A10, Mackiewicz J10, Schadendorff D11, Jaeger D12, Korman AJ13, Bahjat K14, Maio M15, Calabro L15, Teng MW16, Smyth MJ16, Eggermont A17, Robert C18, Kroemer G19, Zitvogel L20.Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25.Cell Res. 2015 Jan 13

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    2015-09-04 zhaozhouchifen

    #Cell#

    0

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    2015-03-15 lisa438

    #个体化医疗#

    0

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    2015-10-24 维他命

    #CEL#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1869009, encodeId=580e186900919, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Sep 04 07:10:00 CST 2015, time=2015-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1929105, encodeId=e78a192910557, content=<a href='/topic/show?id=19d521285fb' target=_blank style='color:#2F92EE;'>#个体化医疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21285, encryptionId=19d521285fb, topicName=个体化医疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373b263, createdName=lisa438, createdTime=Sun Mar 15 22:10:00 CST 2015, time=2015-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959260, encodeId=0c08195926005, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Oct 24 16:10:00 CST 2015, time=2015-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969860, encodeId=907d196986093, content=<a href='/topic/show?id=027a55636c5' target=_blank style='color:#2F92EE;'>#抗肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55636, encryptionId=027a55636c5, topicName=抗肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5bc315, createdName=Tommy1949, createdTime=Thu Dec 10 13:10:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435297, encodeId=7740143529e4b, content=<a href='/topic/show?id=9a5c212e88f' target=_blank style='color:#2F92EE;'>#个体化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21278, encryptionId=9a5c212e88f, topicName=个体化)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521461, encodeId=8c9c15214612b, content=<a href='/topic/show?id=0e108281e8f' target=_blank style='color:#2F92EE;'>#肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82817, encryptionId=0e108281e8f, topicName=肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=995711357332, createdName=drwjr, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557725, encodeId=6871155e725aa, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14801, encodeId=29da1480164, content=副作用也不小, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.122.248.**, createdTime=Wed Jan 28 23:31:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14762, encodeId=a88a14e620e, content=很不错，值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38811612474, createdName=LX004, createdTime=Wed Jan 28 15:47:00 CST 2015, time=2015-01-28, status=1, ipAttribution=)]
    2015-12-10 Tommy1949

    #抗肿瘤免疫疗法#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1869009, encodeId=580e186900919, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Sep 04 07:10:00 CST 2015, time=2015-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1929105, encodeId=e78a192910557, content=<a href='/topic/show?id=19d521285fb' target=_blank style='color:#2F92EE;'>#个体化医疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21285, encryptionId=19d521285fb, topicName=个体化医疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373b263, createdName=lisa438, createdTime=Sun Mar 15 22:10:00 CST 2015, time=2015-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959260, encodeId=0c08195926005, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Oct 24 16:10:00 CST 2015, time=2015-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969860, encodeId=907d196986093, content=<a href='/topic/show?id=027a55636c5' target=_blank style='color:#2F92EE;'>#抗肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55636, encryptionId=027a55636c5, topicName=抗肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5bc315, createdName=Tommy1949, createdTime=Thu Dec 10 13:10:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435297, encodeId=7740143529e4b, content=<a href='/topic/show?id=9a5c212e88f' target=_blank style='color:#2F92EE;'>#个体化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21278, encryptionId=9a5c212e88f, topicName=个体化)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521461, encodeId=8c9c15214612b, content=<a href='/topic/show?id=0e108281e8f' target=_blank style='color:#2F92EE;'>#肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82817, encryptionId=0e108281e8f, topicName=肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=995711357332, createdName=drwjr, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557725, encodeId=6871155e725aa, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14801, encodeId=29da1480164, content=副作用也不小, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.122.248.**, createdTime=Wed Jan 28 23:31:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14762, encodeId=a88a14e620e, content=很不错，值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38811612474, createdName=LX004, createdTime=Wed Jan 28 15:47:00 CST 2015, time=2015-01-28, status=1, ipAttribution=)]
    2015-01-30 zhouqu_8

    #个体化#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1869009, encodeId=580e186900919, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Sep 04 07:10:00 CST 2015, time=2015-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1929105, encodeId=e78a192910557, content=<a href='/topic/show?id=19d521285fb' target=_blank style='color:#2F92EE;'>#个体化医疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21285, encryptionId=19d521285fb, topicName=个体化医疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373b263, createdName=lisa438, createdTime=Sun Mar 15 22:10:00 CST 2015, time=2015-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959260, encodeId=0c08195926005, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Oct 24 16:10:00 CST 2015, time=2015-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969860, encodeId=907d196986093, content=<a href='/topic/show?id=027a55636c5' target=_blank style='color:#2F92EE;'>#抗肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55636, encryptionId=027a55636c5, topicName=抗肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5bc315, createdName=Tommy1949, createdTime=Thu Dec 10 13:10:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435297, encodeId=7740143529e4b, content=<a href='/topic/show?id=9a5c212e88f' target=_blank style='color:#2F92EE;'>#个体化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21278, encryptionId=9a5c212e88f, topicName=个体化)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521461, encodeId=8c9c15214612b, content=<a href='/topic/show?id=0e108281e8f' target=_blank style='color:#2F92EE;'>#肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82817, encryptionId=0e108281e8f, topicName=肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=995711357332, createdName=drwjr, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557725, encodeId=6871155e725aa, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14801, encodeId=29da1480164, content=副作用也不小, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.122.248.**, createdTime=Wed Jan 28 23:31:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14762, encodeId=a88a14e620e, content=很不错，值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38811612474, createdName=LX004, createdTime=Wed Jan 28 15:47:00 CST 2015, time=2015-01-28, status=1, ipAttribution=)]
    2015-01-30 drwjr

    #肿瘤免疫疗法#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1869009, encodeId=580e186900919, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Sep 04 07:10:00 CST 2015, time=2015-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1929105, encodeId=e78a192910557, content=<a href='/topic/show?id=19d521285fb' target=_blank style='color:#2F92EE;'>#个体化医疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21285, encryptionId=19d521285fb, topicName=个体化医疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373b263, createdName=lisa438, createdTime=Sun Mar 15 22:10:00 CST 2015, time=2015-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959260, encodeId=0c08195926005, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Oct 24 16:10:00 CST 2015, time=2015-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969860, encodeId=907d196986093, content=<a href='/topic/show?id=027a55636c5' target=_blank style='color:#2F92EE;'>#抗肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55636, encryptionId=027a55636c5, topicName=抗肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5bc315, createdName=Tommy1949, createdTime=Thu Dec 10 13:10:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435297, encodeId=7740143529e4b, content=<a href='/topic/show?id=9a5c212e88f' target=_blank style='color:#2F92EE;'>#个体化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21278, encryptionId=9a5c212e88f, topicName=个体化)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1521461, encodeId=8c9c15214612b, content=<a href='/topic/show?id=0e108281e8f' target=_blank style='color:#2F92EE;'>#肿瘤免疫疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82817, encryptionId=0e108281e8f, topicName=肿瘤免疫疗法)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=995711357332, createdName=drwjr, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557725, encodeId=6871155e725aa, content=<a href='/topic/show?id=d2601533982' target=_blank style='color:#2F92EE;'>#Research#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Fri Jan 30 03:10:00 CST 2015, time=2015-01-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14801, encodeId=29da1480164, content=副作用也不小, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.122.248.**, createdTime=Wed Jan 28 23:31:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14762, encodeId=a88a14e620e, content=很不错，值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38811612474, createdName=LX004, createdTime=Wed Jan 28 15:47:00 CST 2015, time=2015-01-28, status=1, ipAttribution=)]
    2015-01-30 yangshch

    #Research#

    0

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    2015-01-28 42.122.248.**

    副作用也不小

    0

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    2015-01-28 LX004

    很不错，值得学习

    0