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Chemical Complementarities of Neuroblastoma Tumor-Resident TCR CDR3s and CMV Antigens are Associated with a Better
Kasey L Rigby1, Rahul Jain2, Etienne C Gozlan2
1University of Central Florida College of Medicine, Orlando, FL, 32827, USA.
Abstract:
A likely immune response to a virus can be detected via the presence of TCR CDR3s that (a) exactly match CDR3s known to bind viral antigens or (b) represent chemical complementarity to viral antigens. Previous studies, based on genomics approaches to characterizing anti-CMV TCR CDR3s in patient blood samples, have indicated the possibility that a systemic CMV infection is associated with worse outcomes for NBL, as well as for breast cancer. Thus, the association of NBL tumor-resident anti-CMV TCR CDR3s and patient outcomes was evaluated here, with results indicating that high levels of chemical complementarity between tumor-resident TCR CDR3s and CMV antigens represented a better outcome. This is in apparent contrast to results obtained via the previous study of blood sourced, anti-CMV TCR CDR3s representing a worse outcome. This study identified gene expression values associated with the tumor-specific anti-CMV TCR CDR3s, representing exact matches to known anti-CMV TCR CDR3s, which may assist in identifying a potential underlying mechanism effecting the better outcomes associated with the tumor-resident, anti-CMV TCR CDR3s. Overall, results here raise the question of whether an anti-CMV response directly against the tumor, or within the tumor microenvironment, is involved in reductions in tumor progression or responsiveness to treatment?
Insights
High levels of complementarity between tumor-resident T-cell receptor (TCR) CDR3s and cytomegalovirus (CMV) antigens correlate with better outcomes in neuroblastoma (NBL). This contrasts with previous findings suggesting worse outcomes with blood-based anti-CMV TCR CDR3s.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Immune responses to viruses can be identified by T-cell receptor (TCR) CDR3 sequences that either match known viral antigen-binding CDR3s or exhibit chemical complementarity to viral antigens.
- Previous genomics studies of anti-cytomegalovirus (CMV) TCR CDR3s in blood suggested a link between systemic CMV infection and poorer outcomes in neuroblastoma (NBL) and breast cancer.
Purpose of the Study:
- To investigate the association between NBL tumor-resident anti-CMV TCR CDR3s and patient outcomes.
- To explore potential mechanisms underlying the observed associations by identifying gene expression patterns related to tumor-specific anti-CMV TCR CDR3s.
Main Methods:
- Analysis of TCR CDR3 sequences within NBL tumors.
- Assessment of chemical complementarity between tumor-resident TCR CDR3s and CMV antigens.
- Correlation of TCR CDR3 characteristics with patient outcomes.
- Identification of gene expression values linked to tumor-specific anti-CMV TCR CDR3s.
Main Results:
- High levels of chemical complementarity between tumor-resident TCR CDR3s and CMV antigens were associated with better patient outcomes.
- This finding contrasts with previous studies of blood-derived anti-CMV TCR CDR3s, which indicated worse outcomes.
- Gene expression patterns associated with tumor-specific TCR CDR3s (exact matches) were identified, potentially explaining the improved outcomes.
Conclusions:
- The presence and characteristics of anti-CMV TCR CDR3s within the tumor microenvironment may play a significant role in NBL prognosis.
- Tumor-directed or tumor microenvironment-resident anti-CMV immune responses might contribute to reduced tumor progression or enhanced treatment response.
- Further research is needed to elucidate the precise mechanisms by which anti-CMV immune responses within the tumor influence NBL outcomes.
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