Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44

Amy L. Cummings; Jaklin Gukasyan; Henry Y. LuTristan GroganGemalene SungaCharlene M. FaresNicholas HornsteinJesse ZaretskyJames CarrollBenjamin BachrachWisdom O. AkingbemiDebory LiZorawar NoorAaron LisbergJonathan W. GoldmanDavid ElashoffAlex A. T. BuiAntoni RibasSteven M. DubinettMaura RossettiEdward B. Garon

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Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44

机译：突变景观影响免疫疗法结果在非小细胞肺癌患者癌症与人类白细胞抗原超类型B44

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Human leukocyte antigen (HLA)-B has been recognized as a major determinant of discrepancies in disease outcomes, and recent evidence indicates a role in immune checkpoint blockade (ICB) efficacy. The B44 supertype, which features an electropositive binding pocket that preferentially displays peptides with negatively charged amino acid anchors, is associated with improved survival in ICB-treated melanoma. Yet this effect was not seen in ICB-treated non-small-cell lung cancer (NSCLC). Here we show that mutations leading to glutamic acid substitutions occur more often in melanoma than NSCLC based on mutational landscape. We additionally show stratifying B44 based on the presence of somatic mutations that lead to negatively charged glutamic acid anchors identifies patients with NSCLC with an ICB benefit similar to that seen in melanoma. We anticipate these findings could improve assessment of HLA-related outcomes and prediction of ICB benefit in those with B44, representing approximately half of the world's population.

机译：人类白细胞抗原(HLA) - b公认的主要决定因素差异在疾病的结果,和最近的证据表明在免疫检查点封锁(ICB)效力。功能一个阳性结合口袋优先显示肽与消极带电氨基酸锚,是联系在一起的改善生存ICB-treated黑色素瘤。这种效应在ICB-treated未见非小细胞肺癌(NSCLC)。突变导致谷氨酸替换在黑色素瘤比更容易发生非小细胞肺癌基于突变景观。此外显示分层B44基于体细胞突变导致的存在带负电荷的谷氨酸锚银行独立委员会与非小细胞肺癌患者的识别类似于在黑色素瘤中获益。预测这些发现可以改善HLA-related评估结果和预测银行独立委员会受益的那些B44,代表大约世界人口的一半。

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《Nature cancer.》 |2020年第12期|1167-1175|共9页
作者
Amy L. Cummings; Jaklin Gukasyan; Henry Y. LuTristan GroganGemalene SungaCharlene M. FaresNicholas HornsteinJesse ZaretskyJames CarrollBenjamin BachrachWisdom O. AkingbemiDebory LiZorawar NoorAaron LisbergJonathan W. GoldmanDavid ElashoffAlex A. T. BuiAntoni RibasSteven M. DubinettMaura RossettiEdward B. Garon;
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Department of Medicine, David Geffen School of Medicine at the University of California, Los;

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正文语种英语
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Non-Small-Cell Lung Carcinoma; Melanoma; Lung CancerSomatic Mutationworld populationGlutamic Acidnegative chargeBoat anchorsPatients;

机译：非小细胞肺癌;黑色素瘤肺CancerSomatic Mutationworld populationGlutamicAcidnegative chargeBoat anchorsPatients;

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4. Adu; Aged;; Aged, 80 and over;; Antineoplastic Agents;; Carcinoma, Non-Small-Cell Lung;; Cisplatin;; Cohort Studies;; Deoxycytidine;; Female;; Humans;; Lung Neoplasms;; Male;; Middle Aged;; Mitomycin;; Neoadjuvant Therapy;; Neoplasm Staging;; Pneumonectomy;; Retrospective Studies;; Treatment Outcome;; Vinblastine;; *成年人;; 老年人;; 老年人, 80以上;; 抗肿瘤药;; 癌, 非小细胞肺;; 顺铂;; 队列研究;; 脱氧胞苷;; 肺肿瘤;; 肿瘤辅助疗法;; 肿瘤分期;; 肺切除术;; 回顾性研究;; 治疗结果;; 长春碱 [J] . Clinical cancer research: an official journal of the American Association for Cancer Research . 2009,第18期

机译：Adu; Aged;; Aged, 80 and over;; Antineoplastic Agents;; Carcinoma, Non-Small-Cell Lung;; Cisplatin;; Cohort Studies;; Deoxycytidine;; Female;; Humans;; Lung Neoplasms;; Male;; Middle Aged;; Mitomycin;; Neoadjuvant Therapy;; Neoplasm Staging;; Pneumonectomy;; Retrospective Studies;; Treatment Outcome;; Vinblastine;; *成年人;; 老年人;; 老年人, 80以上;; 抗肿瘤药;; 癌, 非小细胞肺;; 顺铂;; 队列研究;; 脱氧胞苷;; 肺肿瘤;; 肿瘤辅助疗法;; 肿瘤分期;; 肺切除术;; 回顾性研究;; 治疗结果;; 长春碱

Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44

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