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Worse Wilms' Tumor Outcomes Associated With Chemical Complementarity for Multiple T-Cell Receptor CDR3-CMV Epitope
Kasey L Rigby1, Michael J Diaz2, Etienne C Gozlan2
1University of Central Florida College of Medicine, Orlando, FL, U.S.A.
Background/Aim:
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.
Materials And Methods:
We considered recently developed adaptive immune receptor, genomics and bioinformatics approaches to assess the potential impact of cytomegalovirus (CMV) infections in Wilms' tumor.
Results:
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.
Conclusion:
Overall, we present a potentially novel method to assess CMV infections and identify patients who could benefit from therapies that address such infections.
Insights
Cytomegalovirus (CMV) infections may be linked to poorer outcomes in pediatric Wilms' tumors. Analyzing T-cell receptor sequences suggests a novel method to identify patients who could benefit from CMV-targeted therapies.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Wilms' tumors are common pediatric kidney cancers with generally good prognoses.
- Viral infections are implicated in neoplasm development and may influence cancer survival rates.
Purpose of the Study:
- To investigate the potential impact of cytomegalovirus (CMV) infections on Wilms' tumor outcomes.
- To explore novel bioinformatics approaches for assessing viral influence in pediatric cancers.
Main Methods:
- Utilized adaptive immune receptor, genomics, and bioinformatics techniques.
- Compared T-cell receptor (TCR) complementarity determining region-3 (CDR3) sequences from Wilms' tumor specimens against known anti-CMV TCR CDR3s.
- Applied a chemical complementarity scoring method between Wilms' tumor TCR CDR3s and CMV antigens.
Main Results:
- Wilms' tumor cases with anti-CMV TCR CDR3s showed worse overall outcomes.
- Higher chemical complementarity between tumor TCR CDR3s and CMV antigens correlated with poorer outcomes.
- This suggests a potential link between CMV infection and adverse Wilms' tumor progression.
Conclusions:
- Presents a novel method for assessing CMV infections in Wilms' tumor patients.
- Identifies a potential biomarker for stratifying patients who may benefit from anti-CMV therapies.
- Highlights the importance of considering viral factors in pediatric cancer treatment strategies.
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