An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes.
An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes.
复制标题
DOI：
10.3389/fimmu.2017.01566
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Eklund AC
中科院分区：
文献类型：
--
作者：
Bjerregaard AM;Nielsen M;Jurtz V;Barra CM;Hadrup SR;Szallasi Z;Eklund AC
癌症免疫疗法（例如治疗性疫苗和过继性 T 细胞疗法）的个性化可能受益于有效识别和靶向患者特异性新表位。然而，目前基于表位加工和呈递的测序和预测的新表位预测方法导致验证率较低，这表明肽免疫原性的决定因素尚不清楚。我们收集了源自单氨基酸取代的人类新肽的已发表数据，这些新肽的 T 细胞反应性已通过实验测试，包括免疫原性和非免疫原性新肽。在来自 13 篇出版物的 1,948 个新肽-HLA（人类白细胞抗原）组合中，据报道有 53 个可引发 T 细胞反应。从这些数据中，我们发现长度为 9 的肽之间的反应富集。尽管已根据假定的免疫原性可能性预先选择了肽，但我们使用 NetMHCpan-4.0 发现，与非免疫原性肽相比，预测免疫原性新肽与 HLA 的结合明显更强。对免疫原性肽的 HLA 结合强度的研究表明，绝大多数（96%）与 HLA 具有非常强的预测结合，并且结合强度与对病原体衍生表位观察到的结合强度相当。最后，我们发现，在新肽和正常肽具有相当的预测结合强度的情况下，新肽与自身的差异是免疫原性的预测因子。总之，这些结果提出了优先考虑突变肽的新策略，但需要新的数据来证实其价值。
Personalization of cancer immunotherapies such as therapeutic vaccines and adoptive T-cell therapy may benefit from efficient identification and targeting of patient-specific neoepitopes. However, current neoepitope prediction methods based on sequencing and predictions of epitope processing and presentation result in a low rate of validation, suggesting that the determinants of peptide immunogenicity are not well understood. We gathered published data on human neopeptides originating from single amino acid substitutions for which T cell reactivity had been experimentally tested, including both immunogenic and non-immunogenic neopeptides. Out of 1,948 neopeptide-HLA (human leukocyte antigen) combinations from 13 publications, 53 were reported to elicit a T cell response. From these data, we found an enrichment for responses among peptides of length 9. Even though the peptides had been pre-selected based on presumed likelihood of being immunogenic, we found using NetMHCpan-4.0 that immunogenic neopeptides were predicted to bind significantly more strongly to HLA compared to non-immunogenic peptides. Investigation of the HLA binding strength of the immunogenic peptides revealed that the vast majority (96%) shared very strong predicted binding to HLA and that the binding strength was comparable to that observed for pathogen-derived epitopes. Finally, we found that neopeptide dissimilarity to self is a predictor of immunogenicity in situations where neo- and normal peptides share comparable predicted binding strength. In conclusion, these results suggest new strategies for prioritization of mutated peptides, but new data will be needed to confirm their value.
登录
查看更多内容
影响因子：
12.3
作者：
Nielsen M;Andreatta M
通讯作者：
Andreatta M
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：
10.1
作者：
Fritsch EF;Rajasagi M;Ott PA;Brusic V;Hacohen N;Wu CJ
通讯作者：
Wu CJ
影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
影响因子：
56.9
作者：
Stronen, Erlend;Toebes, Mireille;Schumacher, Ton N.
通讯作者：
Schumacher, Ton N.