A scoring system for the electrostatic complementarities of T‐cell receptors and cancer‐mutant amino acids: multi‐cancer analyses of associated survival rates. Issue 4 (21st January 2020)

• Record Type: Journal Article
• Authors: Chobrutskiy, Boris I.; Yeagley, Michelle; Diviney, Andrea; Zaman, Saif; Gozlan, Etienne C.; Tipping, Price; Koohestani, Darush M.; Roca, Andrea M.; Blanck, George
• Is Part Of: Immunology. Volume 159:Issue 4(2020)
• Page Start: 373
• Page End: 383
• Publication Date: 2020-01-21
• Subjects: antigen electrostatic complementarity -- biochemical features -- bioinformatics -- cancer survival outcomes -- mutant amino acids -- T‐cell receptor CDR3; Immunology -- Periodicals
• DOI: 10.1111/imm.13165
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: 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. Abstract : The algorithms developed and tested in this report represent assessments of chemical complementarities of T‐cell receptor CDR3s and mutant amino acids, whereby complementary relationships are associated with better survival.