Blood:HLA-B-21二态性可决定急性髓系白血病免疫疗法的临床预后

2019-02-09 MedSci MedSci原创

NK细胞的功能受杀伤性免疫球蛋白样受体家族(KIRs)和NKG2A/CD94异二聚体这类的抑制性受体调孔。这些受体识别候选靶细胞上的I类HLA同源分子;最近有研究表明,在编码先导肽的基因片段中-21位置上的HLA-B的二态性决定了NK细胞的调控主要是依赖KIRs还是NKG2A/CD94受体。但HLA-B二态性对NK细胞介导的白血病细胞破坏或白血病进程的影响尚不明确。在本研究中,Alexander

NK细胞的功能受杀伤性免疫球蛋白样受体家族(KIRs)和NKG2A/CD94异二聚体这类的抑制性受体调孔。这些受体识别候选靶细胞上的I类HLA同源分子;最近有研究表明,在编码先导肽的基因片段中-21位置上的HLA-B的二态性决定了NK细胞的调控主要是依赖KIRs还是NKG2A/CD94受体。

但HLA-B二态性对NK细胞介导的白血病细胞破坏或白血病进程的影响尚不明确。在本研究中,Alexander Hallner等人通过IL2激活的NK细胞和急性髓系白血病(AML)患者的白血病细胞将携带HLA-B-21M或HLA-B-21T的个体的NK细胞的功能进行比较。

携带HLA-B-21M的受试者的NKG2A+ NK细胞发育的更好一些,并对KIR配体匹配的原发性白血病细胞具有更好的去颗粒降解颗粒的能力。

此外,研究人员还在IV期试验(患者接受以IL2为基础的免疫疗法)中评估了HLA-B-21突变对AML病程的潜在影响。结果显示HLA-B-21M或可提高NK细胞的功能;携带HLA-B-21M的患者的无白血病存活率和总体存活率均优于携带HLA-B-21T的患者。

因此,研究人员推断,HLA-B-21位点的遗传变异可能可以决定活化的NK细胞的抗白血病活性以及活化NK细胞的免疫疗法的临床疗效。


原始出处:

Alexander Hallner, et al. The HLA-B -21 dimorphism impacts on NK cell education and clinical outcome of immunotherapy in acute myeloid leukemia.Blood 2019 :blood-2018-09-874990; doi: https://doi.org/10.1182/blood-2018-09-874990 

本文系梅斯医学(MedSci)原创编译,转载需授权!

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=2005919, encodeId=992d200591924, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Fri May 10 14:51:00 CST 2019, time=2019-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822082, encodeId=0f31182208285, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Thu Nov 28 05:51:00 CST 2019, time=2019-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502055, encodeId=97af1502055a2, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534732, encodeId=c0541534e322d, content=<a href='/topic/show?id=6be9230842e' target=_blank style='color:#2F92EE;'>#临床预后#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23084, encryptionId=6be9230842e, topicName=临床预后)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72412536387, createdName=budeshao, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=2005919, encodeId=992d200591924, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Fri May 10 14:51:00 CST 2019, time=2019-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822082, encodeId=0f31182208285, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Thu Nov 28 05:51:00 CST 2019, time=2019-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502055, encodeId=97af1502055a2, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534732, encodeId=c0541534e322d, content=<a href='/topic/show?id=6be9230842e' target=_blank style='color:#2F92EE;'>#临床预后#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23084, encryptionId=6be9230842e, topicName=临床预后)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72412536387, createdName=budeshao, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=2005919, encodeId=992d200591924, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Fri May 10 14:51:00 CST 2019, time=2019-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822082, encodeId=0f31182208285, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Thu Nov 28 05:51:00 CST 2019, time=2019-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502055, encodeId=97af1502055a2, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534732, encodeId=c0541534e322d, content=<a href='/topic/show?id=6be9230842e' target=_blank style='color:#2F92EE;'>#临床预后#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23084, encryptionId=6be9230842e, topicName=临床预后)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72412536387, createdName=budeshao, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=)]
    2019-02-11 marongnuan
  4. [GetPortalCommentsPageByObjectIdResponse(id=2005919, encodeId=992d200591924, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8944, encryptionId=37b78944ac, topicName=HLA-B)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=606c2500035, createdName=ms3153534357578991, createdTime=Fri May 10 14:51:00 CST 2019, time=2019-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822082, encodeId=0f31182208285, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Thu Nov 28 05:51:00 CST 2019, time=2019-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502055, encodeId=97af1502055a2, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8941, encryptionId=14a6894190, topicName=HLA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e72c9501412, createdName=marongnuan, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534732, encodeId=c0541534e322d, content=<a href='/topic/show?id=6be9230842e' target=_blank style='color:#2F92EE;'>#临床预后#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23084, encryptionId=6be9230842e, topicName=临床预后)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72412536387, createdName=budeshao, createdTime=Mon Feb 11 13:51:00 CST 2019, time=2019-02-11, status=1, ipAttribution=)]

相关资讯

Blood:CSF1R抑制剂通过阻断支持细胞的旁分泌信号抑制急性髓系白血病细胞

中心点:CSF1R在支持细胞亚群中表达,其抑制可降低超过20%的AML患者样本的细胞活性。CSF1R活性刺激旁路细胞因子分泌,或可作为AML支持细胞的新治疗靶点。摘要:为明确AML的新的治疗靶点,研究人员对原发性AML患者样本进行小分子和siRNA筛选。在23%的样本中,研究人员发现了对CSF1R抑制的敏感性,CSF1R是一种受体酪氨酸激酶,调控髓系细胞的存活、增殖和分化。对CSF1R抑制剂GW-

Lancet Oncol:单药应用时,奎轧替尼能否为FLT3 ITD阳性复发难治AML带来获益?

高龄和FLT3-ITD突变AML患者常和早期复发和较差预后相关,目前尚无有效的治疗药物。新一代 FLT3抑制剂奎轧替尼(Quizartinib)可有效治疗复发难治性急性髓系白血病,且耐受性良好。一项多中心2期临床试验探讨了奎轧替尼单药治疗R/R AML的疗效及安全性,其结果于近期发表在Lancet oncology上。

Blood:选择性自噬受体p62缺失可延缓白血病进展

中心点:选择性自噬受体p62缺失会影响白血病小鼠模型的白血病进展。p62与白血病细胞的线粒体结合,对通过自噬有效清除受损线粒体必不可少。摘要:自噬可维持造血干细胞的完整性,防止恶性转化。除了批量降解外,选择性自噬还作为细胞内的质量控制机制,借助p62 (SQSTM1)等自噬受体特异性地将泛素化的载体运转到自噬体中。The Duy Nguyen等人对p62在急性髓系白血病(AML)和AML小鼠模型中

Blood:双功能的PD-1xαCD33xαCD33融合蛋白可逆转急性髓系白血病的适应性免疫逃逸

靶向CD33的双特异性T细胞衔接器(BiTER)AMG330,在体外和小鼠模型中均被证明可高效调节急性髓系白血病(AML)细胞的细胞溶解。但T细胞激活与PD-L1和AML细胞上的其他抑制检查点上调相关,而PD-L1和抑制检查点上调又会导致适应性免疫耐受。PD1和PD-L1阻滞剂或许可中和T细胞功能障碍,但是,这会导致广泛的免疫相关的副反应(irAEs)。Monika Herrmann等人开发出一种

JCO:洛莫司汀联合化疗改善老年AML患者的生存?LAM-SA 2007全新结果公布

老年AML患者在AML发病人群中占绝大多数,中位总生存期(OS)不到1年。一直以来,如何改善老年AML患者的不良预后始终为临床研究的热门话题。烷化剂洛莫司汀可通过调节DNA损伤修复起到显著的抗白血病效应,那么在传统化疗中联合洛莫司汀治疗是否改善预后?近日,JCO杂志发表了LAM-SA 2007临床试验最新结果。

关注|老年急性髓系白血病治疗新拐点

近十年来,急性髓系白血病(AML)的治疗已取得较大进步。但与年轻AML取得的治疗进展相比,老年AML患者由于存在高龄、合并疾病多、不良染色体核型多、前驱血液系统疾病等不利预后因素,近年来疗效并未得到明显改善。近几年,美国血液病学会年会(ASH)、欧洲血液病学会年会(EHA)、美国临床肿瘤学会年会(ASCO)等国际会议报道的临床研究数据显示,一种口服B淋巴细胞瘤-2基因(BCL-2)抑制剂——Ven