Nature Cancer:非小细胞肺癌免疫疗法效果预测标志物-HLA-B44超型

2020-12-31 精准医学资讯网 Bio生物世界

人类白细胞抗原(HLA)-B被认为是疾病预后差异的主要决定因素,最近有证据表明其在免疫检查点阻断疗法(ICB)的疗效中起作用。研究发现HLA-B44超型可用于NSCLC免疫治疗疗效预测。

人类白细胞抗原(HLA)-B被认为是疾病预后差异的主要决定因素,最近有证据表明其在免疫检查点阻断疗法(ICB)的疗效中起作用。HLA-B44超型,其特点是具有电正性结合的口袋,优先展示带负电荷的氨基酸锚定肽,与提高黑色素瘤ICB治疗的生存率有关1。然而,在ICB治疗的非小细胞肺癌(NSCLC)中却没有看到这种相关性。

加州大学洛杉矶分校 Edward Garon 团队在 Nature Cancer 杂志发表了题为:Mutational landscape influences immunotherapy outcomes among patients with non-small-celllung cancer with human leukocyte antigen supertype B44 的研究论文,探讨了HLA-B44超型是否影响免疫检查点阻断疗法(ICB)在非小细胞肺癌中的疗效2。
该研究表明,基于基因突变图谱,突变导致谷氨酸替代在黑色素瘤中比非小细胞肺癌更常发生。此外,基于导致负电荷谷氨酸锚位点点的体细胞突变的存在对B44进行分层,确定了非小细胞肺癌患者的免疫检查点阻断治疗获益与黑色素瘤相似。预计这些发现可以改善评估HLA相关的结果和预测B44患者的免疫检查点阻断治疗获益。

研究团队对加州大学洛杉矶分校(UCLA)的67例经帕姆单抗治疗的晚期NSCLC患者进行全外显子测序(WES),获得HLA分型、肿瘤突变负荷(TMB)以及新生抗原等,并用Dana Farber癌症研究所的NSCLC和黑色素瘤免疫治疗队列作为外部验证。此外,研究者通过体外试验分析HLA-B44超型与新生抗原间的半抑制浓度(IC50)。

研究发现HLA-B44超型在UCLA-NSCLC、DF-NSCLC,以及DF-黑色素瘤队列中都可以有效预测ICB治疗的PFS和OS,携带HLA-B44超型的患者的PFS和OS均长于未携带者。



基于带电新表位基序的OS和PFS分析

HLA-B44超型对NSCLC和黑色素瘤免疫治疗预后影响

总之,研究发现HLA-B44超型可用于NSCLC免疫治疗疗效预测,与其在黑色素瘤中功能类似,但其他HLA超型还有待进一步验证。

原始出处:

Amy L. Cummings, Jaklin Gukasyan, Henry Y. Lu, et al.Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44.Nature Cancer.volume 1, pages1167–1175(2020)

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  5. [GetPortalCommentsPageByObjectIdResponse(id=2005921, encodeId=2e9a20059213a, content=<a href='/topic/show?id=37b78944ac' target=_blank style='color:#2F92EE;'>#HLA-B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, 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 Sep 17 12:27:40 CST 2021, time=2021-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884886, encodeId=4b4d188488676, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue May 11 03:27:40 CST 2021, time=2021-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1841616, encodeId=48701841616e1, content=<a href='/topic/show?id=18bf61953d3' target=_blank style='color:#2F92EE;'>#标志物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61953, encryptionId=18bf61953d3, topicName=标志物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Mon Oct 11 02:27:40 CST 2021, time=2021-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059953, encodeId=d6c6205995322, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sat Nov 20 19:27:40 CST 2021, time=2021-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502071, encodeId=a7b515020e1f0, content=<a href='/topic/show?id=14a6894190' target=_blank style='color:#2F92EE;'>#HLA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, 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=Sat Jan 02 02:27:40 CST 2021, time=2021-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=912813, encodeId=7cfc9128133b, content=已学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201225/6e1ef4f864494d0284b9282bc4cafc19/f7f10a42767b46c9823f11c34f905873.jpg, createdBy=145f5447474, createdName=ms6000001700483633, createdTime=Fri Jan 01 07:22:29 CST 2021, time=2021-01-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047253, encodeId=347e104e253c6, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Thu Dec 31 14:27:40 CST 2020, time=2020-12-31, status=1, ipAttribution=)]
    2021-01-02 marongnuan
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    2021-01-01 ms6000001700483633

    已学习

    0

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    2020-12-31 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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