Worse Wilms' Tumor Outcomes Associated With Chemical Complementarity for Multiple T-Cell Receptor CDR3-CMV Epitope Pairs.

Abstract

Wilms' tumors are pediatric renal tumors that generally have a good prognosis and outcomes. Viral illnesses have been linked to development of neoplasms and should be considered as a factor that could modulate overall survival. We considered recently developed adaptive immune receptor, genomics and bioinformatics approaches to assess the potential impact of cytomegalovirus (CMV) infections in Wilms' tumor. T-cell receptor (TCR) complementarity determining region-3 (CDR3) amino acid sequences from Wilms' tumor specimens represented by the Therapeutically Applicable Research to Generate Effective Treatments dataset were compared with known anti-CMV TCR CDR3s, indicating that cases representing the anti-CMV TCR CDR3s had worse outcomes. Then, a chemical complementarity scoring approach for the Wilms' tumor, TCR CDR3s and a series of CMV antigens further indicated that cases representing a higher chemical complementarity to the CMV antigens had worse outcomes. Overall, we present a potentially novel method to assess CMV infections and identify patients who could benefit from therapies that address such infections.