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Published on: February 8, 2020
TCR CDR3-CMV Antigen Chemical Complementaries Are Associated With a Worse Outcome for Renal Cell Carcinoma
Lila Alkassab1, Michael J Diaz1, Elizabeth A Fletcher1
1Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, U.S.A.
Background/Aim:
Due to still unresolved questions regarding viruses as either a primary cause or a comorbidity in cancer, we examined a potential immune response to cytomegalovirus (CMV) in the renal cell carcinoma (RCC) setting using genomics and bioinformatics approaches.
Materials And Methods:
Specifically, we assessed chemical complementarity scores (CSs) for solid tissue normal resident, T-cell receptor (TCR) complementarity determining region 3 (CDR3s) and CMV antigens and determined whether higher or lower CS groups were associated with a higher or lower survival probability.
Results:
This was indeed the case, with all such analyses consistently indicating a lower overall and progression-free survival for the cases representing the higher TCR CDR3-CMV antigen chemical CSs. This basic result was obtained for two separate RCC datasets and multiple CMV antigens.
Conclusion:
The results raise the question, to what extent a systemic CMV infection may represent an important co-morbidity for RCC.
Insights
Cytomegalovirus (CMV) infection may worsen survival in renal cell carcinoma (RCC). Higher T-cell receptor (TCR) complementarity determining region 3 (CDR3)-CMV antigen interactions correlate with poorer outcomes in RCC patients.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- The role of viruses as a cause or comorbidity in cancer remains unclear.
- Investigating cytomegalovirus (CMV) immune response in renal cell carcinoma (RCC) is crucial.
Purpose of the Study:
- To examine the potential immune response to CMV in RCC.
- To determine the association between T-cell receptor (TCR) complementarity determining region 3 (CDR3)-CMV antigen interactions and patient survival.
Main Methods:
- Genomic and bioinformatics approaches were utilized.
- Chemical complementarity scores (CSs) between TCR CDR3s and CMV antigens were assessed.
- Correlation between CS groups and survival probability was analyzed.
Main Results:
- Higher TCR CDR3-CMV antigen CSs were consistently associated with lower overall and progression-free survival.
- This finding was replicated across two independent RCC datasets.
- Multiple CMV antigens were analyzed, yielding consistent results.
Conclusions:
- Systemic CMV infection may represent a significant comorbidity in RCC.
- The immune response to CMV warrants further investigation in the context of RCC prognosis.
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