Chemical complementarity between immune receptors and cancer mutants, independent of antigen presentation protein binding, is associated with increased survival rates

• Main Authors: Monica Hsiang, Boris I. Chobrutskiy, Michael Diaz, Taha I. Huda, Stefan Creadore, Saif Zaman, Konrad J. Cios, Etienne C. Gozlan, George Blanck
• Format: Article
• Language: English
• Published: Elsevier 2021-06-01
• Series: Translational Oncology
• Subjects: uterine cancer immunogenomics; TCR-mutant amino acid complementarity scoring; complementarity determining region-3
• Online Access: http://www.sciencedirect.com/science/article/pii/S1936523321000619

Uterine cancer has been associated with a T-cell immune response that leads to increased survival. Therefore, we used several bioinformatics approaches to explore specific interactions between T-cell receptor (TCR) and tumor mutant peptide sequences. Using endometrioid uterine cancer exome files from the The Cancer Genome Atlas database, we obtained tumor resident V-J recombinations for the T-Cell Receptor alpha gene (TRA). The charged-based, chemical complementarity for each patient's LRP2 or TTN mutant amino acids (AAs) and the recovered, TRA complementarity determining region-3 (CDR3) sequences was calculated, allowing a division of patients into complementary and noncomplementary groups. Complementary groups with TTN mutants had increased disease-free survival and increased expression of complement genes. Furthermore, the survival distinction based on CDR3-mutant peptide complementarity was independent of programmatically assessed HLA class II binding and was not observable based on the CDR3 AA chemical features alone. The above approach provides a potential, highly efficient method for identifying TCR targets in uterine cancer and may aid in the development of novel prognostic tools.