Chemical complementarity between immune receptor CDR3s and IDH1 mutants correlates with increased survival for lower grade glioma.,Oncogene

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Chemical complementarity between immune receptor CDR3s and IDH1 mutants correlates with increased survival for lower grade glioma.
Oncogene ( IF 6.9 ) Pub Date : 2019-11-18 , DOI: 10.1038/s41388-019-1101-2
Boris I Chobrutskiy ₁ , Michelle Yeagley ₁ , Price Tipping ₁ , Saif Zaman _{1,

2} , Andrea Diviney ₁ , Dhruv N Patel ₁ , Shayan Falasiri ₁ , Vladimir N Uversky ₁ , George Blanck _{1,

2}

Affiliation

Focusing on highly specific aspects of the immune response is likely to answer a number of basic questions, and in some cases even resolve basic contradictions, in cancer immunology. For example, there are many cases, where chronic inflammation is associated with cancer development, and many other cases where an immune response represents an anticancer process. In this study, using bioinformatics algorithms, we examined the chemical relationships between the amino acid sequences of the complementarity-determining region-3 (CDR3) represented by immune receptors associated with lower grade glioma and isocitrate dehydrogenase-1 (IDH1) mutants. In particular, we developed a chemical complementarity scoring approach to classify tumors based on the complementarity of CDR3s and mutant IDH1 amino acids, relying on net charge per residue and hydropathy parameters. There was a strong correlation between the increased survival in low-grade glioma (LGG) and complementarity of IDH1 mutants to the CDR3 domain of the T-cell receptor beta chain (TRB). Similar results were obtained for TRB CDR3s and NRAS mutants in melanoma. Furthermore, the clear connection between increased survival rates and immune receptor-IDH1 mutant complementarities may also, partially, explain the better LGG prognosis for patients with IDH1 mutants.

中文翻译：

免疫受体 CDR3s 和 IDH1 突变体之间的化学互补性与低级别胶质瘤的存活率增加相关。

关注免疫反应的高度特异性方面可能会回答癌症免疫学中的许多基本问题，在某些情况下甚至可以解决基本矛盾。例如，在许多情况下，慢性炎症与癌症的发展有关，还有许多其他情况下，免疫反应代表了抗癌过程。在这项研究中，我们使用生物信息学算法检查了由与低级别胶质瘤和异柠檬酸脱氢酶-1 (IDH1) 突变体相关的免疫受体代表的互补决定区 3 (CDR3) 的氨基酸序列之间的化学关系。特别是，我们开发了一种化学互补性评分方法，根据 CDR3 和突变 IDH1 氨基酸的互补性对肿瘤进行分类，依赖于每残留物的净电荷和亲水性参数。低级别胶质瘤 (LGG) 的存活率增加与 IDH1 突变体与 T 细胞受体β链 (TRB) 的 CDR3 结构域的互补性之间存在很强的相关性。黑色素瘤中的 TRB CDR3 和 NRAS 突变体获得了类似的结果。此外，存活率增加与免疫受体-IDH1 突变体互补性之间的明确联系也可以部分解释 IDH1 突变体患者的 LGG 预后更好。

更新日期：2019-11-18

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