J Immunother Cancer:营养与健康所等揭示中药复方苦参注射液增敏索拉菲尼治疗肝癌新机制

2020-03-31 佚名 中国生物技术网

该研究表明,中药复方苦参注射液通过TNFR1解除肿瘤免疫微环境中的肿瘤相关巨噬细胞(TAMs)引起的免疫抑制,从而增敏低剂量索拉菲尼的肝癌治疗效果,为肝癌的临床治疗提供了新策略。

近日,肿瘤免疫治疗学会(The Society for Immunotherapy of Cancer, SITC)会刊Journal for ImmunoTherapy of Cancer 在线发表了中国科学院上海营养与健康研究所及上海交通大学公共卫生学院王慧研究组的研究论文“Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib”,该研究表明,中药复方苦参注射液通过TNFR1解除肿瘤免疫微环境中的肿瘤相关巨噬细胞(TAMs)引起的免疫抑制,从而增敏低剂量索拉菲尼的肝癌治疗效果,为肝癌的临床治疗提供了新策略。

肝细胞癌是一种恶性程度较高的肿瘤,其死亡率占全球第四位。索拉菲尼作为第一个靶向肝癌细胞的化学药物,是临床上用于晚期肝癌患者的一线治疗药物。但是由于药物引起的毒副作用、继发性耐药、肿瘤异质性以及抑制性肿瘤免疫微环境等原因,仅有30%的患者具有有效的治疗效果。肿瘤免疫治疗在临床上取得的巨大成功为肝癌的临床治疗带来了曙光。TAMs作为肿瘤免疫微环境中重要的炎性细胞之一,参与了肿瘤的发生发展、侵袭和转移等过程,与肿瘤血管生成和免疫抑制密切相关。因此,靶向肿瘤微环境中的肿瘤相关巨噬细胞重塑肿瘤微环境,成为肿瘤治疗领域的研究热点。

复方苦参注射液在临床上被批准用于治疗癌症引起的疼痛。前期研究表明复方苦参注射液能提高肝动脉插管化疗栓塞的治疗效果,但复方苦参注射液在调节肝癌免疫微环境以及肝癌治疗方面仍不清楚。在本研究中,博士研究生杨阳等在研究员王慧、副研究员巴乾和研究员杨成华的指导下,通过体内和体外实验发现复方苦参注射液通过抑制促肿瘤M2-TAMs的浸润及分化,提高抗肿瘤M1-TAMs的浸润及分化,从而增加肿瘤微环境中的CD8+T细胞数量并增强CD8+T细胞的肿瘤杀伤能力,同时降低CD8+T细胞的功能耗竭来维持持续的免疫杀伤活性。作为免疫调节剂,复方苦参注射液增敏低剂量索拉菲尼的肝癌治疗效果,抑制肝癌复发,并降低索拉菲尼的肝脏毒性。机制研究揭示复方苦参注射液靶向TAMs表面TNFR1及其介导的NF-κB/P65、P38/MAPK信号转导促进抗肿瘤M1-TAMs的分化,进而激活CD8+T细胞的抗肿瘤活性。综上,该研究揭示了复方苦参注射液抗肝癌的作用机制,表明传统中药复方作为免疫调节剂与化疗药物联合使用可能是肝癌治疗的一种新策略。

该工作由中科院营养与健康所和上海交通大学公共卫生学院合作完成。营养与健康所博士研究生杨阳为该论文第一作者,王慧、巴乾和杨成华为共同通讯作者,该项工作得到国家重点研发计划等的支持。

图:复方苦参注射液增敏索拉菲尼抗肝癌作用机制

原始出处:Yang Y, Sun M, Yao W, et al. Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib. J Immunother Cancer. 2020 Mar;8(1).

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    2020-08-26 zhaojie88

    中药#复方苦参注射液#通过TNFR1解除肿瘤免疫#微环境#中的肿瘤相关巨噬细胞(TAMs)引起的免疫抑制,

    0

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  4. [GetPortalCommentsPageByObjectIdResponse(id=813598, encodeId=efe0813598c7, content=中药<a href='/topic/show?id=d85242655e3' target=_blank style='color:#2F92EE;'>#复方苦参注射液#</a>通过TNFR1解除肿瘤免疫<a href='/topic/show?id=430750648d8' target=_blank style='color:#2F92EE;'>#微环境#</a>中的肿瘤相关巨噬细胞(TAMs)引起的免疫抑制,, beContent=null, objectType=article, channel=null, level=null, likeNumber=188, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42655, encryptionId=d85242655e3, topicName=复方苦参注射液), TopicDto(id=50648, encryptionId=430750648d8, topicName=微环境)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Aug 26 22:40:00 CST 2020, time=2020-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085581, encodeId=5300208558114, content=<a href='/topic/show?id=542188113f6' target=_blank style='color:#2F92EE;'>#营养与健康所#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88113, encryptionId=542188113f6, topicName=营养与健康所)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Mon Apr 13 21:26:22 CST 2020, time=2020-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1976513, encodeId=e85019e6513b6, content=<a href='/topic/show?id=cc758e026bd' target=_blank style='color:#2F92EE;'>#苦参注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87026, encryptionId=cc758e026bd, topicName=苦参注射液)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Aug 11 11:26:22 CST 2020, time=2020-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1344634, encodeId=1bc3134463482, content=<a href='/topic/show?id=af96e69750b' target=_blank style='color:#2F92EE;'>#索拉菲尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76975, encryptionId=af96e69750b, topicName=索拉菲尼)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d2f42500210, createdName=12498ef1m31(暂无昵称), createdTime=Wed Apr 01 21:26:22 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586584, encodeId=6e8515865849a, content=<a href='/topic/show?id=f87c6499085' target=_blank style='color:#2F92EE;'>#注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64990, encryptionId=f87c6499085, topicName=注射液)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c93417353045, createdName=shijzhiewnjhch, createdTime=Wed Apr 01 21:26:22 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039213, encodeId=d48110392132c, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Mar 31 09:26:22 CST 2020, time=2020-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040273, encodeId=278010402e388, content=肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=留走人康, createdTime=Tue Mar 31 09:26:22 CST 2020, time=2020-03-31, status=1, ipAttribution=)]
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  6. [GetPortalCommentsPageByObjectIdResponse(id=813598, encodeId=efe0813598c7, content=中药<a href='/topic/show?id=d85242655e3' target=_blank style='color:#2F92EE;'>#复方苦参注射液#</a>通过TNFR1解除肿瘤免疫<a href='/topic/show?id=430750648d8' target=_blank style='color:#2F92EE;'>#微环境#</a>中的肿瘤相关巨噬细胞(TAMs)引起的免疫抑制,, beContent=null, objectType=article, channel=null, level=null, likeNumber=188, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42655, encryptionId=d85242655e3, topicName=复方苦参注射液), TopicDto(id=50648, encryptionId=430750648d8, topicName=微环境)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Aug 26 22:40:00 CST 2020, time=2020-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085581, encodeId=5300208558114, content=<a href='/topic/show?id=542188113f6' target=_blank style='color:#2F92EE;'>#营养与健康所#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88113, encryptionId=542188113f6, topicName=营养与健康所)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7387164, createdName=zhangj7108, createdTime=Mon Apr 13 21:26:22 CST 2020, time=2020-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1976513, encodeId=e85019e6513b6, content=<a href='/topic/show?id=cc758e026bd' target=_blank style='color:#2F92EE;'>#苦参注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87026, encryptionId=cc758e026bd, topicName=苦参注射液)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Aug 11 11:26:22 CST 2020, time=2020-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1344634, encodeId=1bc3134463482, content=<a href='/topic/show?id=af96e69750b' target=_blank style='color:#2F92EE;'>#索拉菲尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76975, encryptionId=af96e69750b, topicName=索拉菲尼)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d2f42500210, createdName=12498ef1m31(暂无昵称), createdTime=Wed Apr 01 21:26:22 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586584, encodeId=6e8515865849a, content=<a href='/topic/show?id=f87c6499085' target=_blank style='color:#2F92EE;'>#注射液#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64990, encryptionId=f87c6499085, topicName=注射液)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c93417353045, createdName=shijzhiewnjhch, createdTime=Wed Apr 01 21:26:22 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039213, encodeId=d48110392132c, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Mar 31 09:26:22 CST 2020, time=2020-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040273, encodeId=278010402e388, content=肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=留走人康, createdTime=Tue Mar 31 09:26:22 CST 2020, time=2020-03-31, status=1, ipAttribution=)]
    2020-03-31 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

    0

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    2020-03-31 留走人康

    肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负

    0

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