NeoScore Integrates Characteristics of the Neoantigen:MHC Class I Interaction and Expression to Accurately Prioritize Immunogenic Neoantigens.
NeoScore Integrates Characteristics of the Neoantigen:MHC Class I Interaction and Expression to Accurately Prioritize Immunogenic Neoantigens.
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DOI：
10.4049/jimmunol.2100700
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发表时间：
2022-04-01
期刊：
影响因子：
--
通讯作者：
Hastings KT
中科院分区：
文献类型：
--
作者：
Borden ES;Ghafoor S;Buetow KH;LaFleur BJ;Wilson MA;Hastings KT
免疫原性新抗原的准确优先顺序是开发个性化癌症疫苗和区分可能对免疫检查点抑制有反应的患者的关键。然而，对于哪些特征最能预测新抗原免疫原性尚未达成共识，迄今为止还没有模型既具有高敏感性和特异性，又与免疫治疗后的生存率显着相关。我们通过以下方式解决了免疫原性新抗原优先顺序中的这些挑战：1）确定哪些新抗原特征最能预测免疫原性，2）将这些特征整合到免疫原性评分（NeoScore）中，3）证明 NeoScore 与免疫检查点抑制反应中的生存率显着相关。使用用于特征选择的正则化回归模型对来自经过验证的数据集的一千个随机且均匀分布的免疫原性和非免疫原性新抗原组合进行分析。选定的特征、新抗原：MHC I 类复合物的解离常数和结合稳定性以及肿瘤中突变基因的表达均被整合到 NeoScore 中。提供了一个网络应用程序来计算 NeoScore。与之前的模型相比，NeoScore 在四个测试数据集中获得了改进或相当的性能，通过灵敏度、特异性和接收者操作员特征曲线下面积来衡量。在接受免疫检查点抑制治疗的皮肤黑色素瘤患者中，较高的最大 NeoScore 与改善的生存率相关。总体而言，NeoScore 有潜力改善个性化疫苗开发的新抗原优先顺序，并有助于确定哪些患者可能对免疫治疗产生反应。
Accurate prioritization of immunogenic neoantigens is key to developing personalized cancer vaccines and distinguishing those patients likely to respond to immune checkpoint inhibition. However, there is no consensus regarding which characteristics best predict neoantigen immunogenicity, and no model to date has both high sensitivity and specificity and a significant association with survival in response to immunotherapy. We address these challenges in the prioritization of immunogenic neoantigens by 1) identifying which neoantigen characteristics best predict immunogenicity, 2) integrating these characteristics into an immunogenicity score, the NeoScore, and 3) demonstrating a significant association of the NeoScore with survival in response to immune checkpoint inhibition. One thousand random and evenly split combinations of immunogenic and non-immunogenic neoantigens from a validated dataset were analyzed using a regularized regression model for characteristic selection. The selected characteristics, the dissociation constant and binding stability of the neoantigen:MHC class I complex and expression of the mutated gene in the tumor, were integrated into the NeoScore. A web application is provided for calculation of the NeoScore. The NeoScore results in improved, or equivalent, performance in four test datasets as measured by sensitivity, specificity, and area under the receiver operator characteristics curve compared to previous models. Among cutaneous melanoma patients treated with immune checkpoint inhibition, a high maximum NeoScore was associated with improved survival. Overall, the NeoScore has the potential to improve neoantigen prioritization for the development of personalized vaccines and contribute to the determination of which patients are likely to respond to immunotherapy.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.
影响因子：
14.9
作者：
Fairley, Susan;Lowy-Gallego, Ernesto;Flicek, Paul
通讯作者：
Flicek, Paul
癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
通讯作者：
Linette GP