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Detection of Anti-CMV TCR CDR3s via Blood and Tumor Exome Files Correlates With Increased Survival for Stomach
Utsav Kapoor1, Michael T Aboujaoude1, Konrad J Cios1
1Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Abstract:
While the role of anti-cytomegalovirus (CMV) T-cell responses in the cancer setting is becoming increasingly recognized, the association between CMV and survival outcomes has not been subject to study through more recent immunogenomic approaches. Thus for this study, we extracted T-cell receptor (TCR) recombination reads from whole exome sequencing (WXS) and RNA sequencing (RNAseq) files of stomach adenocarcinoma (STAD) and soft tissue sarcoma (SARC) samples from the Cancer Genome Atlas (TCGA) and matched the corresponding TCR complementarity determining region-3 (CDR3) amino acid (AA) sequences represented by these reads to known anti-CMV CDR3 sequences. Results indicated that the recovery of both TRA and TRB recombination reads from WXS files, from either blood or tumor samples, which corresponded to AA sequences matching anti-CMV CDR3s, correlated with better survival probabilities for both STAD and SARC. However, TCR CDR3s represented by recombination reads recovered from RNAseq files and matching anti-CMV TCR CDR3 AA sequences correlated with lower survival probabilities. These results raise the question of whether exposure to CMV prior to onset or progression of cancer may lead to better survival probability whereas a potentially active T-cell response to CMV during cancer onset or progression could represent an ongoing comorbidity? In conclusion, TCR CDR3s may be an important indicator of prognosis for stomach cancer and soft tissue sarcoma and may support further research into anti-CMV CDR3s as a tool for development of immunotherapy for these cancers.
Insights
Cytomegalovirus (CMV) T-cell receptor (TCR) sequences detected via whole exome sequencing correlate with better survival in stomach and soft tissue cancers. However, CMV TCRs found via RNA sequencing suggest poorer outcomes, prompting further research.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- The role of anti-cytomegalovirus (CMV) T-cell responses in cancer is increasingly recognized.
- Immunogenomic approaches have not been extensively used to study the association between CMV and cancer survival outcomes.
Purpose of the Study:
- To investigate the association between cytomegalovirus (CMV) T-cell receptor (TCR) sequences and survival outcomes in stomach adenocarcinoma (STAD) and soft tissue sarcoma (SARC) using immunogenomic methods.
- To explore the potential prognostic value of anti-CMV TCR complementarity determining region-3 (CDR3) amino acid (AA) sequences.
Main Methods:
- Extracted T-cell receptor (TCR) recombination reads from whole exome sequencing (WXS) and RNA sequencing (RNAseq) data of STAD and SARC samples from The Cancer Genome Atlas (TCGA).
- Matched TCR complementarity determining region-3 (CDR3) amino acid (AA) sequences to known anti-CMV CDR3 sequences.
- Correlated the presence of anti-CMV TCR CDR3 sequences with patient survival probabilities.
Main Results:
- Recovery of anti-CMV TCR CDR3 sequences from WXS data (blood or tumor) correlated with better survival in both STAD and SARC.
- Detection of anti-CMV TCR CDR3 sequences from RNAseq data correlated with lower survival probabilities in both cancer types.
- These findings suggest a dichotomy based on the sequencing method, possibly indicating prior CMV exposure versus active CMV response during cancer.
Conclusions:
- TCR CDR3 sequences, particularly those targeting CMV, may serve as important prognostic indicators for STAD and SARC.
- Further research into anti-CMV CDR3 sequences could aid in developing novel immunotherapies for these cancers.
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