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

Oncogene. 2020 Feb;39(8):1773-1783. doi: 10.1038/s41388-019-1101-2. Epub 2019 Nov 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Complementarity Determining Regions / genetics*
  • Complementarity Determining Regions / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism*
  • Kaplan-Meier Estimate
  • Mutation*
  • Neoplasm Grading

Substances

  • Complementarity Determining Regions
  • Isocitrate Dehydrogenase
  • IDH1 protein, human