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A scoring system for the electrostatic complementarities of T-cell receptors and cancer-mutant amino acids: multi-cancer analyses of associated survival rates.
Immunology ( IF 6.4 ) Pub Date : 2020-01-21 , DOI: 10.1111/imm.13165
Boris I Chobrutskiy 1 , Michelle Yeagley 1 , Andrea Diviney 1 , Saif Zaman 1 , Etienne C Gozlan 1 , Price Tipping 1 , Darush M Koohestani 1 , Andrea M Roca 1 , George Blanck 1, 2
Affiliation  

The anti‐tumor immune response is considered to be due to the T‐cell receptor (TCR) binding to tumor antigens, which can be either wild‐type, early stem cell proteins, presumably foreign to a developed immune system; or mutant peptides, foreign to the immune system because of a mutant amino acid (aa) or otherwise somatically altered aa sequence. Recently, very large numbers of TCR complementarity‐determining region‐3 (CDR3) aa sequences obtained from tumor specimens have become available. We developed a novel algorithm for assessing the complementarity of tumor mutant peptides and TCR CDR3s, based on the retrieval of TCR CDR3 aa sequences from both tumor specimen and patient blood exomes and by using an automated process of assessing CDR3 and mutant aa electrical charges. Results indicated many instances where high electrostatic complementarity was associated with a higher survival rate. In particular, our approach led to the identification of specific genes contributing significantly to the complementary, TCR CDR3‐mutant aa. These results suggest a novel approach to tumor immunoscoring and may lead to the identification of high‐priority neo‐antigen, peptide vaccines; or to the identification of ex vivo stimulants of tumor‐infiltrating lymphocytes.

中文翻译:

T细胞受体和癌症突变氨基酸的静电互补性评分系统:相关生存率的多癌分析。

抗肿瘤免疫反应被认为是由于T细胞受体(TCR)与肿瘤抗原结合而引起的,该抗原可能是野生型早期干细胞蛋白,可能与发达的免疫系统无关。或突变肽,由于突变氨基酸(aa)或以其他方式被体细胞改变的氨基酸序列而对免疫系统而言是异源的。最近,从肿瘤标本中获得的大量TCR互补决定区3(CDR3)aa序列已经可用。我们基于从肿瘤标本和患者血液外显子组中检索TCR CDR3aa序列,并使用评估CDR3和突变aa电荷的自动化过程,开发了一种用于评估肿瘤突变肽和TCR CDR3s互补性的新颖算法。结果表明,在许多情况下,高静电互补性与更高的存活率相关。尤其是,我们的方法导致鉴定出对互补的TCR CDR3突变氨基酸有重要贡献的特定基因。这些结果表明了一种新的肿瘤免疫评分方法,并可能导致鉴定高优先级的新抗原肽疫苗。或用于鉴定肿瘤浸润淋巴细胞的离体刺激物。
更新日期:2020-03-26
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